3-(1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine and therapeutic uses thereof

ABSTRACT

Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an azaindazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser. No. 15/267,939, filed Sep. 16, 2016, which is acontinuation application of U.S. patent application Ser. No. 14/847,371,filed Sep. 8, 2015, which claims the benefit of U.S. ProvisionalApplication No. 62/047,406, filed Sep. 8, 2014, each of which isincorporated herein by reference in its entirety.

BACKGROUND

Technical Field

This disclosure relates to inhibitors of one or more proteins in the Wntpathway, including inhibitors of one or more Wnt proteins, andcompositions comprising the same. More particularly, it concerns the useof an azaindazole compound or salts or analogs thereof, in the treatmentof disorders characterized by the activation of Wnt pathway signaling(e.g., cancer, abnormal cellular proliferation, angiogenesis, fibroticdisorders, bone or cartilage diseases, and osteoarthritis), themodulation of cellular events mediated by Wnt pathway signaling, as wellas genetic diseases and neurological conditions/disorders/diseases dueto mutations or dysregulation of the Wnt pathway and/or of one or moreof Wnt signaling components. Also provided are methods for treatingWnt-related disease states.

Background

The Wnt growth factor family includes more than 10 genes identified inthe mouse and at least 19 genes identified in the human. Members of theWnt family of signaling molecules mediate many short-and long-rangepatterning processes during invertebrate and vertebrate development. TheWnt signaling pathway is known for its role in the inductiveinteractions that regulate growth and differentiation, and it also playsroles in the homeostatic maintenance of post-embryonic tissue integrity.Wnt stabilizes cytoplasmic β-catenin, which stimulates the expression ofgenes including c-myc, c jun, fra-1, and cyclin D1. In addition,misregulation of Wnt signaling can cause developmental defects and isimplicated in the genesis of several human cancers. The Wnt pathway hasalso been implicated in the maintenance of stem or progenitor cells in agrowing list of adult tissues including skin, blood, gut, prostate,muscle, and the nervous system.

SUMMARY

The present disclosure provides methods and reagents, involvingcontacting a cell with an agent, such as an azaindazole compound, in asufficient amount to antagonize a Wnt activity, e.g., to reverse orcontrol an aberrant growth state or correct a genetic disorder due tomutations in Wnt signaling components.

Some embodiments disclosed herein include Wnt inhibitors containing anazaindazole core. Other embodiments disclosed herein includepharmaceutical compositions and methods of treatment using thesecompounds.

One embodiment disclosed herein includes a compound having the structureof Formula I:

as well as prodrugs and pharmaceutically acceptable salts thereof

In some embodiments of Formula (I):

R¹is selected from the group consisting of —heteroaryl(R⁴)_(q) and—heterocyclyl(R⁵)_(h);

R² is selected from the group consisting of H and halide;

R³ is selected from the group consisting of —heteroaryl(R⁶)_(q),—heterocyclyl(R⁷), and —aryl(R⁸)_(k);

each R⁴ is one substituent attached to the heteroaryl and isindependently selected from the group consisting of halide, —(C₁₋₆alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R⁹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹¹)_(k),—NHC(═O)R¹², —NR¹³R¹⁴, —(C₁₋₆ alkylene)NR¹⁵R^(16,) and —OR²²;

each R⁵ is one substituent attached to the heterocyclyl and isindependently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN;

each R⁶ is one substituent attached to the heteroaryl and isindependently selected from the group consisting of —(C₁₋₆ alkyl),halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁷;

each R⁷ is one substituent attached to the heterocyclyl and isindependently selected from the group consisting of —(C₁₋₆ alkyl),halide, —CF₃, —CN, and —OCH₃;

each R⁸ is one substituent attached to the aryl and is independentlyselected from the group consisting of —(C₁₋₆ alkyl), halide, —CF₃, —CN,—OCH₃, —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁷, —NR¹³(C₁₋₆ alkylene)NR¹³R¹⁴, —(C₁₋₆alkylene)_(p)NR¹³R¹⁴; and —OR²⁵;

each R⁹ is one substituent attached to the heterocyclyl and isindependently selected from the group consisting of amino, —(C₁₋₄alkyl), halide, —CF₃, and —CN;

each R¹⁰ is one substituent attached to the carbocyclyl and isindependently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN;

each R¹¹is one substituent attached to the aryl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN;

each R¹² is independently selected from the group consisting of —(C₁₋₉alkyl), —heteroaryl(R¹⁸)_(q), —aryl(R¹⁹)_(k), —CH₂aryl(R¹⁹)_(k),—carbocyclyl(R²⁰)_(j), —CH₂carbocyclyl(R²⁰)_(j), —(C₁₋₄alkylene)_(p)NR²³R²⁴, —heterocyclyl(R²¹)_(h), and—CH₂heterocyclyl(R²¹)_(h);

each R¹³ is independently selected from the group consisting of H and—(C₁₋₆ alkyl);

each R¹⁴ is independently selected from the group consisting of H,—(C₁₋₆ alkyl), —CH₂aryl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j);

each R¹⁵ is independently selected from the group consisting of H and—(C₁₋₆ alkyl);

each R¹⁶ is independently selected from the group consisting of H,—(C₁₋₆ alkyl), —CH₂aryl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j);

each R¹⁷ is a —(C₁₋₆ alkyl);

each R¹⁸ is one substituent attached to the heteroaryl and isindependently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN;

each R¹⁹ is one substituent attached to the aryl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN;

each R²⁰ is one substituent attached to the carbocyclyl and isindependently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN;

each R²¹is one substituent attached to the heterocyclyl and isindependently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN;

each R²² is independently selected from the group consisting of H,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²¹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R²⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹⁹)_(k),and —(C₁₋₆ alkylene)_(p)NR23R²⁴;

each R²³ is independently selected from the group consisting of H and—(C₁₋₆ alkyl);

each R²⁴ is independently selected from the group consisting of H and—(C₁₋₆ alkyl);

each R²⁵ is independently selected from the group consisting of H,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²¹)_(h), and —(C₁₋₆alkylene)_(p)NR²³R²⁴;

each p is independently 0 or 1;

each q is independently 0 to 4;

each h is independently 0 to 10;

each k is independently 0 to 5; and

each j is independently 0 to 12.

Some embodiments include stereoisomers and pharmaceutically acceptablesalts of a compound of Formula (I).

Some embodiments include pro-drugs of a compound of Formula (I).

Some embodiments of the present disclosure include pharmaceuticalcompositions comprising a compound of Formula (I) and a pharmaceuticallyacceptable carrier, diluent, or excipient.

Other embodiments disclosed herein include methods of inhibiting one ormore members of the Wnt pathway, including one or more Wnt proteins byadministering to a patient affected by a disorder or disease in whichaberrant Wnt signaling is implicated, such as cancer and other diseasesassociated with abnormal angiogenesis, cellular proliferation, cellcycling and mutations in Wnt signaling components, a compound accordingto Formula (I). Accordingly, the compounds and compositions providedherein can be used to treat cancer, to reduce or inhibit angiogenesis,to reduce or inhibit cellular proliferation and correct a geneticdisorder due to mutations in Wnt signaling components.

Non-limiting examples of diseases which can be treated with thecompounds and compositions provided herein include a variety of cancers,diabetic retinopathy, pulmonary fibrosis, rheumatoid arthritis, sepsis,ankylosing spondylitis, psoriasis, scleroderma, mycotic and viralinfections, osteochondrodysplasia, Alzheimer's disease, lung disease,bone/osteoporotic (wrist, spine, shoulder and hip) fractures, articularcartilage (chondral) defects, degenerative disc disease (orintervertebral disc degeneration), polyposis coli,osteoporosis-pseudoglioma syndrome, familial exudativevitreoretinopathy, retinal angiogenesis, early coronary disease,tetra-Amelia syndrome, MUllerian-duct regression and virilization,SERKAL syndrome, diabetes mellitus type 2, Fuhrmann syndrome,Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication syndrome, tooth agenesis, Wilms tumor, skeletaldysplasia, focal dermal hypoplasia, autosomal recessive anonychia,neural tube defects, alpha-thalassemia (ATRX) syndrome, fragile Xsyndrome, ICF syndrome, Angelman syndrome, Prader-Willi syndrome,Beckwith-Wiedemann Syndrome, Norrie disease, and Rett syndrome.

Some embodiments of the present disclosure include methods to preparecompounds of Formula (I).

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the invention, as claimed.

DETAILED DESCRIPTION

Provided herein are compositions and methods for inhibiting one or moremembers of the Wnt pathway, including one or more Wnt proteins. OtherWnt inhibitors and methods for using the same are disclosed in U.S.application Ser. Nos. 12/852,706; 12/968,505; 13/552,188; 13/800,963;13/855,874; 13/887,177 13/938,691; 13/938,692; 14/019,103; 14/019,147;14/019,940; 14/149,948; 14/178,749; 14/331,427; and 14/334,005; and U.S.Provisional Application Ser. Nos. 61/232,603;61/288,544; 61/305,459;61/620,107; 61/642,915; and 61/750,221, all of which are incorporated byreference in their entirety herein.

Some embodiments provided herein relate to a method for treating adisease or disorder including, but not limited to, cancers, diabeticretinopathy, pulmonary fibrosis, rheumatoid arthritis, sepsis,ankylosing spondylitis, psoriasis, scleroderma, mycotic and viralinfections, bone and cartilage diseases, Alzheimer's disease, lungdisease, osteoarthritis, bone/osteoporotic (wrist, spine, shoulder andhip) fractures, articular cartilage (chondral) defects, degenerativedisc disease (or intervertebral disc degeneration), polyposis coli, bonedensity and vascular defects in the eye (Osteoporosis-pseudogliomaSyndrome, OPPG) and other eye diseases or syndromes associated withdefects or damaged photoreceptors, familial exudative vitreoretinopathy,retinal angiogenesis, early coronary disease, tetra-amelia,Müllerian-duct regression and virilization, SERKAL syndrome, type IIdiabetes, Fuhrmann syndrome, Al-Awadi/Raas-Rothschild/Schinzelphocomelia syndrome, odonto-onycho-dermal dysplasia, obesity,split-hand/foot malformation, caudal duplication, tooth agenesis, Wilmstumor, skeletal dysplasia, focal dermal hypoplasia, autosomal recessiveanonychia, neural tube defects, alpha-thalassemia (ATRX) syndrome,fragile X syndrome, ICF syndrome, Angelman's syndrome, Prader-Willisyndrome, Beckwith-Wiedemann Syndrome, Norrie disease, and Rettsyndrome.

In some embodiments, non-limiting examples of bone and cartilagediseases which can be treated with the compounds and compositionsprovided herein include bone spur (osteophytes), craniosynostosis,fibrodysplasia ossificans progressive, fibrous dysplasia, giant celltumor of bone, hip labral tear, meniscal tears, bone/osteoporotic(wrist, spine, shoulder and hip) fractures, articular cartilage(chondral) defects, degenerative disc disease (or intervertebral discdegeneration), osteochondritis dissecans, osteochondroma (bone tumor),osteopetrosis, relapsing polychondritis, and Salter-Harris fractures.

In some embodiments, pharmaceutical compositions are provided that areeffective for treatment of a disease of an animal, e.g., a mammal,caused by the pathological activation or mutations of the Wnt pathway.The composition includes a pharmaceutically acceptable carrier and acompound as described herein.

Definitions

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as is commonly understood by one of ordinary skillin the art to which this disclosure belongs. All patents, applications,published applications, and other publications are incorporated byreference in their entirety. In the event that there is a plurality ofdefinitions for a term herein, those in this section prevail unlessstated otherwise.

As used herein, “alkyl” means a branched, or straight chain chemicalgroup containing only carbon and hydrogen, such as methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, sec-pentyl and neo-pentyl. Alkyl groups can eitherbe unsubstituted or substituted with one or more substituents. Alkylgroups can be saturated or unsaturated (e.g., containing —C═C— or —C≡C—subunits), at one or several positions. In some embodiments, alkylgroups include 1to 9 carbon atoms (for example, 1to 6 carbon atoms, 1to4 carbon atoms, or 1to 2 carbon atoms).

As used herein, “alkylene” means a bivalent branched, or straight chainchemical group containing only carbon and hydrogen, such as methylene,ethylene, n-propylene, iso-propylene, n-butylene, iso-butylene,sec-butylene, tert-butylene, n-pentylene, iso-pentylene, sec-pentyleneand neo-pentylene. Alkylene groups can either be unsubstituted orsubstituted with one or more substituents. Alkylene groups can besaturated or unsaturated (e.g., containing —C═C— or —C≡C— subunits), atone or several positions. In some embodiments, alkylene groups include1to 9 carbon atoms (for example, 1to 6 carbon atoms, 1to 4 carbon atoms,or 1to 2 carbon atoms).

As used herein, “carbocyclyl” means a cyclic ring system containing onlycarbon atoms in the ring system backbone, such as cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, and cyclohexenyl. Carbocyclyls mayinclude multiple fused rings. Carbocyclyls may have any degree ofsaturation provided that at least one ring in the ring system is notaromatic. Carbocyclyl groups can either be unsubstituted or substitutedwith one or more substituents. In some embodiments, carbocyclyl groupsinclude 3 to 10 carbon atoms, for example, 3 to 6 carbon atoms.

As used herein, “lower alkyl” means a subset of alkyl having 1to 3carbon atoms, which is linear or branched. Examples of lower alkylsinclude methyl, ethyl, n-propyl and isopropyl. Likewise, radicals usingthe terminology “lower” refer to radicals having 1to about 3 carbons inthe alkyl portion of the radical.

As used herein, “aryl” means a mono-, bi-, tri- or polycyclic group withonly carbon atoms present in the ring backbone having 5 to 14 ringatoms, alternatively 5, 6, 9, or 10 ring atoms; and having 6, 10, or 14pi electrons shared in a cyclic array; wherein at least one ring in thesystem is aromatic. Aryl groups can either be unsubstituted orsubstituted with one or more substituents. Examples of aryl includephenyl, naphthyl, tetrahydronaphthyl, 2,3-dihydro-1H-indenyl, andothers. In some embodiments, the aryl is phenyl.

As used herein, “arylalkyl” means an aryl-alkyl- group in which the aryland alkyl moieties are as previously described. In some embodiments,arylalkyl groups contain a C₁₋₄alkyl moiety. Exemplary arylalkyl groupsinclude benzyl and 2-phenethyl.

As used herein, the term “heteroaryl” means a mono-, bi-, tri- orpolycyclic group having 5 to 14 ring atoms, alternatively 5, 6, 9, or 10ring atoms; and having 6, 10, or 14 pi electrons shared in a cyclicarray; wherein at least one ring in the system is aromatic, and at leastone ring in the system contains one or more heteroatoms independentlyselected from the group consisting of N, O, and S. Heteroaryl groups caneither be unsubstituted or substituted with one or more substituents.Examples of heteroaryl include thienyl, pyridinyl, furyl, oxazolyl,oxadiazolyl, pyrrolyl, imidazolyl, triazolyl, thiodiazolyl, pyrazolyl,isoxazolyl, thiadiazolyl, pyranyl, pyrazinyl, pyrimidinyl, pyridazinyl,triazinyl, thiazolyl benzothienyl, benzoxadiazolyl, benzofuranyl,benzimidazolyl, benzotriazolyl, cinnolinyl, indazolyl, indolyl,isoquinolinyl, isothiazolyl, naphthyridinyl, purinyl, thienopyridinyl,pyrido[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyridinyl, quinazolinyl,quinolinyl, thieno[2,3-c]pyridinyl, pyrazolo[3,4-b]pyridinyl,pyrazolo[3,4-c]pyridinyl, pyrazolo[4,3-c]pyridine,pyrazolo[4,3-b]pyridinyl, tetrazolyl, chromane,2,3-dihydrobenzo[b][1,4]dioxine, benzo [d][1,3]dioxole,2,3-dihydrobenzofuran, 2,3-dihydrobenzo[b][1,4]oxathiine, and others. Insome embodiments, the heteroaryl is selected from thienyl, pyridinyl,furyl, pyrazolyl, imidazolyl, pyranyl, pyrazinyl, and pyrimidinyl.

As used herein, “halo”, “halide” or “halogen” is a chloro, bromo,fluoro, or iodo atom radical. In some embodiments, a halo is a chloro,bromo or fluoro. For example, a halide can be fluoro.

As used herein, “haloalkyl” means a hydrocarbon substituent, which is alinear or branched, alkyl, alkenyl or alkynyl substituted with one ormore chloro, bromo, fluoro, and/or iodo atom(s). In some embodiments, ahaloalkyl is a fluoroalkyls, wherein one or more of the hydrogen atomshave been substituted by fluoro. In some embodiments, haloalkyls are of1to about 3 carbons in length (e.g., 1to about 2 carbons in length or1carbon in length). The term “haloalkylene” means a diradical variant ofhaloalkyl, and such diradicals may act as spacers between radicals,other atoms, or between a ring and another functional group.

As used herein, “heterocyclyl” means a nonaromatic cyclic ring systemcomprising at least one heteroatom in the ring system backbone.Heterocyclyls may include multiple fused rings. Heterocyclyls may besubstituted or unsubstituted with one or more substituents. In someembodiments, heterocycles have 5-7 members. In six membered monocyclicheterocycles, the heteroatom(s) are selected from one to three of O, Nor S, and wherein when the heterocycle is five membered, it can have oneor two heteroatoms selected from O, N, or S. Examples of heterocyclylinclude azirinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl,1,4,2-dithiazolyl, dihydropyridinyl, 1,3-dioxanyl, 1,4-dioxanyl,1,3-dioxolanyl, morpholinyl, thiomorpholinyl, piperazinyl, pyranyl,pyrrolidinyl, tetrahydrofuryl, tetrahydropyridinyl, oxazinyl, thiazinyl,thiinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isoxazolidinyl,piperidinyl, pyrazolidinyl imidazolidinyl, thiomorpholinyl, and others.In some embodiments, the heterocyclyl is selected from azetidinyl,morpholinyl, piperazinyl, pyrrolidinyl, and tetrahydropyridinyl.

As used herein, “monocyclic heterocyclyl” means a single nonaromaticcyclic ring comprising at least one heteroatom in the ring systembackbone. Heterocyclyls may be substituted or unsubstituted with one ormore substituents. In some embodiments, heterocycles have 5-7 members.In six membered monocyclic heterocycles, the heteroatom(s) are selectedfrom one to three of O, N or S, and wherein when the heterocycle is fivemembered, it can have one or two heteroatoms selected from O, N, or S.Examples of heterocyclyl include azirinyl, aziridinyl, azetidinyl,oxetanyl, thietanyl, 1,4,2-dithiazolyl, dihydropyridinyl, 1,3-dioxanyl,1,4-dioxanyl, 1,3-dioxolanyl, morpholinyl, thiomorpholinyl, piperazinyl,pyranyl, pyrrolidinyl, tetrahydrofuryl, tetrahydropyridinyl, oxazinyl,thiazinyl, thiinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl,isoxazolidinyl, piperidinyl, pyrazolidinyl imidazolidinyl,thiomorpholinyl, and others.

The term “substituted” refers to moieties having substituents replacinga hydrogen on one or more non-hydrogen atoms of the molecule. It will beunderstood that “substitution” or “substituted with” includes theimplicit proviso that such substitution is in accordance with permittedvalence of the substituted atom and the substituent, and that thesubstitution results in a stable compound, e.g., which does notspontaneously undergo transformation such as by rearrangement,cyclization, elimination, etc. Substituents can include, for example,—(C₁₋₉ alkyl) optionally substituted with one or more of hydroxyl, —NH₂,—NH(C₁₋₃ alkyl), and —N(C₁₋₃ alkyl)₂; —(C₁₋₉ haloalkyl); a halide; ahydroxyl; a carbonyl [such as —C(O)OR, and —C(O)R]; a thiocarbonyl [suchas —C(S)OR, —C(O)SR, and —C(S)R]; —(C₁₋₉ alkoxyl) optionally substitutedwith one or more of halide, hydroxyl, —NH₂, —NH(C₁₋₃ alkyl), and —N(C₁₋₃alkyl)₂; —OPO(OH)₂; a phosphonate [such as —PO(OH)₂ and —PO(OR′)₂];—OPO(OR′)R″; —NRR′; —C(O)NRR′; —C(NR)NR′R″; —C(NR′)R″; a cyano; a nitro;an azido; —SH; —S—R; —OSO₂(OR); a sulfonate [such as —SO₂(OH) and—SO₂(OR)]; —SO₂NR′R″; and —SO₂R; in which each occurrence of R, R′ andR″ are independently selected from H; —(C₁₋₉ alkyl); C₆₋₁₀ aryloptionally substituted with from 1-3R″′; 5-10 membered heteroaryl havingfrom 1-4 heteroatoms independently selected from N, O, and S andoptionally substituted with from 1-3 R″′; C₃₋₇ carbocyclyl optionallysubstituted with from 1-3 R″′; and 3-8 membered heterocyclyl having from1-4 heteroatoms independently selected from N, O, and S and optionallysubstituted with from 1-3 R″′; wherein each R″′ is independentlyselected from —(C₁₋₆ alkyl), —(C₁₋₆haloalkyl), a halide (e.g., F), ahydroxyl, —C(O)OR, —C(O)R, —(C₁₋₆ alkoxyl), —NRR′, —C(O)NRR′, and acyano, in which each occurrence of R and R′ is independently selectedfrom H and —(C₁₋₆alkyl). In some embodiments, the substituent isselected from —(C₁₋₆ alkyl), —(C₁₋₆ haloalkyl), a halide (e.g., F), ahydroxyl, —C(O)OR, —C(O)R, —(C₁₋₆ alkoxyl), —NRR′, —C(O)NRR′, and acyano, in which each occurrence of R and R′ is independently selectedfrom H and —(C₁₋₆ alkyl).

As used herein, when two groups are indicated to be “linked” or “bonded”to form a “ring”, it is to be understood that a bond is formed betweenthe two groups and may involve replacement of a hydrogen atom on one orboth groups with the bond, thereby forming a carbocyclyl, heterocyclyl,aryl, or heteroaryl ring. The skilled artisan will recognize that suchrings can and are readily formed by routine chemical reactions. In someembodiments, such rings have from 3-7 members, for example, 5 or 6members.

The skilled artisan will recognize that some structures described hereinmay be resonance forms or tautomers of compounds that may be fairlyrepresented by other chemical structures, even when kinetically, theartisan recognizes that such structures are only a very small portion ofa sample of such compound(s). Such compounds are clearly contemplatedwithin the scope of this disclosure, though such resonance forms ortautomers are not represented herein.

The compounds provided herein may encompass various stereochemicalforms. The compounds also encompass diastereomers as well as opticalisomers, e.g., mixtures of enantiomers including racemic mixtures, aswell as individual enantiomers and diastereomers, which arise as aconsequence of structural asymmetry in certain compounds. Separation ofthe individual isomers or selective synthesis of the individual isomersis accomplished by application of various methods which are well knownto practitioners in the art. Unless otherwise indicated, when adisclosed compound is named or depicted by a structure withoutspecifying the stereochemistry and has one or more chiral centers, it isunderstood to represent all possible stereoisomers of the compound.

The term “administration” or “administering” refers to a method ofproviding a dosage of a compound or pharmaceutical composition to avertebrate or invertebrate, including a mammal, a bird, a fish, or anamphibian, where the method is, e.g., orally, subcutaneously,intravenously, intralymphatic, intranasally, topically, transdermally,intraperitoneally, intramuscularly, intrapulmonarilly, vaginally,rectally, ontologically, neuro-otologically, intraocularly,subconjuctivally, via anterior eye chamber injection, intravitreally,intraperitoneally, intrathecally, intracystically, intrapleurally, viawound irrigation, intrabuccally, intra-abdominally, intra-articularly,intra-aurally, intrabronchially, intracapsularly, intrameningeally, viainhalation, via endotracheal or endobronchial instillation, via directinstillation into pulmonary cavities, intraspinally, intrasynovially,intrathoracically, via thoracostomy irrigation, epidurally,intratympanically, intracisternally, intravascularly,intraventricularly, intraosseously, via irrigation of infected bone, orvia application as part of any admixture with a prosthetic device. Themethod of administration can vary depending on various factors, e.g.,the components of the pharmaceutical composition, the site of thedisease, the disease involved, and the severity of the disease.

A “diagnostic” as used herein is a compound, method, system, or devicethat assists in the identification or characterization of a health ordisease state. The diagnostic can be used in standard assays as is knownin the art.

The term “mammal” is used in its usual biological sense. Thus, itspecifically includes humans, cattle, horses, monkeys, dogs, cats, mice,rats, cows, sheep, pigs, goats, and non-human primates, but alsoincludes many other species.

The term “pharmaceutically acceptable carrier”, “pharmaceuticallyacceptable diluent” or “pharmaceutically acceptable excipient” includesany and all solvents, co-solvents, complexing agents, dispersion media,coatings, isotonic and absorption delaying agents and the like which arenot biologically or otherwise undesirable. The use of such media andagents for pharmaceutically active substances is well known in the art.Except insofar as any conventional media or agent is incompatible withthe active ingredient, its use in the therapeutic compositions iscontemplated. Supplementary active ingredients can also be incorporatedinto the compositions. In addition, various adjuvants such as arecommonly used in the art may be included. These and other such compoundsare described in the literature, e.g., in the Merck Index, Merck &Company, Rahway, N.J. Considerations for the inclusion of variouscomponents in pharmaceutical compositions are described, e.g., in Gilmanet al. (Eds.) (2010); Goodman and Gilman's: The Pharmacological Basis ofTherapeutics, 12th Ed., The McGraw-Hill Companies.

The term “pharmaceutically acceptable salt” refers to salts that retainthe biological effectiveness and properties of the compounds providedherein and, which are not biologically or otherwise undesirable. In manycases, the compounds provided herein are capable of forming acid and/orbase salts by virtue of the presence of amino and/or carboxyl groups orgroups similar thereto. Many such salts are known in the art, forexample, as described in WO 87/05297. Pharmaceutically acceptable acidaddition salts can be formed with inorganic acids and organic acids.Inorganic acids from which salts can be derived include, for example,hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid, and the like. Organic acids from which salts can bederived include, for example, acetic acid, propionic acid, glycolicacid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinicacid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamicacid, mandelic acid, methanesulfonic acid, ethanesulfonic acid,p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceuticallyacceptable base addition salts can be formed with inorganic and organicbases. Inorganic bases from which salts can be derived include, forexample, sodium, potassium, lithium, ammonium, calcium, magnesium, iron,zinc, copper, manganese, aluminum, and the like; particularly preferredare the ammonium, potassium, sodium, calcium, and magnesium salts.Organic bases from which salts can be derived include, for example,primary, secondary, and tertiary amines, substituted amines includingnaturally occurring substituted amines, cyclic amines, basic ionexchange resins, and the like, specifically such as isopropylamine,trimethylamine, diethylamine, triethylamine, tripropylamine, andethanolamine.

“Solvate” refers to the compound formed by the interaction of a solventand a compound as provided herein or a salt thereof Suitable solvatesare pharmaceutically acceptable solvates including hydrates.

“Patient” as used herein, means a human or a non-human mammal, e.g., adog, a cat, a mouse, a rat, a cow, a sheep, a pig, a goat, a non-humanprimate, or a bird, e.g., a chicken, as well as any other vertebrate orinvertebrate. In some embodiments, the patient is a human.

A “therapeutically effective amount” or “pharmaceutically effectiveamount” of a compound as provided herein is one which is sufficient toachieve the desired physiological effect and may vary according to thenature and severity of the disease condition, and the potency of thecompound. “Therapeutically effective amount” is also intended to includeone or more of the compounds of Formula I in combination with one ormore other agents that are effective to treat the diseases and/orconditions described herein. The combination of compounds can be asynergistic combination. Synergy, as described, for example, by Chou andTalalay, Advances in Enzyme Regulation (1984), 22, 27-55, occurs whenthe effect of the compounds when administered in combination is greaterthan the additive effect of the compounds when administered alone as asingle agent. In general, a synergistic effect is most clearlydemonstrated at sub-optimal concentrations of the compounds. It will beappreciated that different concentrations may be employed forprophylaxis than for treatment of an active disease. This amount canfurther depend upon the patient's height, weight, sex, age and medicalhistory.

A therapeutic effect relieves, to some extent, one or more of thesymptoms of the disease.

“Treat,” “treatment,” or “treating,” as used herein refers toadministering a compound or pharmaceutical composition as providedherein for therapeutic purposes. The term “therapeutic treatment” refersto administering treatment to a patient already suffering from a diseasethus causing a therapeutically beneficial effect, such as amelioratingexisting symptoms, ameliorating the underlying metabolic causes ofsymptoms, postponing or preventing the further development of adisorder, and/or reducing the severity of symptoms that will or areexpected to develop.

“Drug-eluting” and/or controlled release as used herein refers to anyand all mechanisms, e.g., diffusion, migration, permeation, and/ordesorption by which the drug(s) incorporated in the drug-elutingmaterial pass therefrom over time into the surrounding body tissue.

“Drug-eluting material” and/or controlled release material as usedherein refers to any natural, synthetic or semi-synthetic materialcapable of acquiring and retaining a desired shape or configuration andinto which one or more drugs can be incorporated and from whichincorporated drug(s) are capable of eluting over time.

“Elutable drug” as used herein refers to any drug or combination ofdrugs having the ability to pass over time from the drug-elutingmaterial in which it is incorporated into the surrounding areas of thebody.

The term “comprising” as used herein is synonymous with “including,”“containing,” or “characterized by,” and is inclusive or open-ended anddoes not exclude additional, unrecited elements or method steps.

Compounds

The compounds and compositions described herein can be used asanti-proliferative agents, e.g., anti-cancer and anti-angiogenesisagents, and/or as inhibitors of the Wnt signaling pathway, e.g., fortreating diseases or disorders associated with aberrant Wnt signaling.In addition, the compounds can be used as inhibitors of one or morekinases, kinase receptors, or kinase complexes. Such compounds andcompositions are also useful for controlling cellular proliferation,differentiation, and/or apoptosis.

Some embodiments of the present disclosure include compounds of FormulaI:

or salts, pharmaceutically acceptable salts, or prodrugs thereof

In some embodiments, R¹is selected from the group consisting of—pyridinyl(R⁴) and —pyrimidinyl(R⁵).

In some embodiments, R¹is selected from the group consisting of—heteroaryl(R⁴)_(q) and —heterocyclyl(R⁵)_(h).

In some embodiments, R¹is selected from the group consisting of—piperidinyl(R⁵)_(h) and —tetrahydropyridinyl(R⁵)_(h).

In some embodiments, R¹is selected from the group consisting of—pyridinyl(R⁴)_(q), —pyrimidinyl(R⁴)_(q), —pyrazinyl(R⁴)_(q),—pyrazolyl(R⁴)_(q), and —imidazolyl(R⁴)_(q).

In some embodiments, R² is selected from the group consisting of H andhalide.

In some embodiments, R³ is selected from the group consisting of—heteroaryl(R⁶)_(q), —heterocyclyl(R⁷)_(h), and —aryl(R⁸)_(k).

In some embodiments, R³ is selected from the group consisting of—pyridinyl(R⁶)_(q), —imidazolyl(R⁶)_(q), —furanyl(R⁶)_(q),—thiophenyl(R⁶)_(q), —piperidinyl(R⁷)_(h), —piperazinyl(R⁷)_(h), and—phenyl(R⁸)_(k).

In some embodiments, R⁴ is one substituent attached to the pyridinyl andis independently selected from the group consisting of H, halide, —(C₁₋₆alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R⁹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹¹)_(k),—NHC(═O)R¹², —NR¹³R¹⁴, and (C₁₋₆ alkylene)NR¹⁵R¹⁶.

In some embodiments, each R⁴ is one substituent attached to theheteroaryl and is independently selected from the group consisting ofhalide, —(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R⁹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹¹)_(k),—NHC(═O)R¹², —NR¹³R¹⁴, —(C₁₋₆ alkylene)NR¹⁵R¹⁶, and —OR²².

In some embodiments, each R⁴ is one substituent attached to theheteroaryl and is independently selected from the group consisting of F,—Me, —Et, —(CH₂)heterocyclyl(R⁹)_(h), —heterocyclyl(R⁹)_(h),—(CH₂)carbocyclyl(R¹⁰)_(j), —(CH₂)aryl(R¹¹)_(k), —NHC(═O)(C₁₋₅ alkyl),—NHC(═O)phenyl(R¹⁹)_(k), —NHC(═O)(CH₂)phenyl(R¹⁹)_(k),—NHC(═O)carbocyclyl(R²⁰)_(j), —NHC(═O)(CH₂)heterocyclyl(R²¹)_(h), —NH₂,—N(C₁₋₃ alkyl)₂, —NH(C₁₋₄ alkyl), —(CH₂)N(C₁₋₃ alkyl)₂, —(CH₂)NH(C₁₋₄alkyl), —OH, —O(C₁₋₃ alkyl), —Ocarbocyclyl(R²⁰)_(j),-Oheterocyclyl(R²¹)_(h), —O(CH₂CH₂)heterocyclyl(R²¹)_(h),—O(CH₂CH₂)N(C₁₋₃ alkyl)₂, and —O(CH₂)phenyl(R¹⁹)_(k).

In some embodiments, R⁵ is one substituent attached to the pyrimidinyland is independently selected from the group consisting of H, halide,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R⁹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹¹)_(k),—NHC(═O)R¹², —NR¹³R¹⁴, and —(C₁₋₆ alkylene)NR¹⁵R¹⁶.

In some embodiments, each R⁵ is one substituent attached to theheterocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R⁶ is one substituent attached to theheteroaryl and is independently selected from the group consisting of H,—(C₁₋₆ alkyl), halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁷.

In some embodiments, each R⁶ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—(C₁₋₆ alkyl), halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁷.

In some embodiments, each R⁶ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—Me, —Et, F, —CF₃, —OCH₃, —CN, and —C(═O)(C₁₋₃ alkyl).

In some embodiments, each R⁷ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofH, —(C₁₋₆ alkyl), halide, —CF₃,—CN, and —OCH3.

In some embodiments, each R⁷ is one substituent attached to theheterocyclyl and is independently selected from the group consisting of—(C₁₋₆ alkyl), halide, —CF₃,—CN, and —OCH3.

In some embodiments, each R⁸ is one substituent attached to the aryl andis independently selected from the group consisting of H, —(C₁₋₆ alkyl),halide, —CF₃, —CN, —OCH₃, —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁷, —NR¹³(C₁₋₆alkylene)NR¹³R¹⁴, and —(C₁₋₆ alkylene)_(p)NR¹³R¹⁴.

In some embodiments, each R⁸ is one substituent attached to the aryl andis independently selected from the group consisting of —(C₁₋₆ alkyl),halide, —CF₃, —CN, —OCH₃, —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁷, —NR¹³(C₁₋₆alkylene)NR¹³R¹⁴, —(C₁₋₆ alkylene)_(p)NR¹³R¹⁴, and —OR²⁵.

In some embodiments, each R⁸ is one substituent attached to the aryl andis independently selected from the group consisting of —Me, —Et, F,—CF₃,—CN, —OCH₃, —(CH₂CH₂)NHSO₂(C₁₋₃ alkyl), —NH(CH₂CH₂)N(C₁₋₃ alkyl)₂,—OH, —O(C₁₋₃ alkyl), —O(CH₂CH₂)heterocyclyl(R²¹)_(h), and—O(CH₂CH₂)N(C₁₋₃ alkyl)₂.

In some embodiments, each R⁹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofH, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R⁹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofamino, —(C₁₋₄ alkyl), halide, —CF₃,and —CN.

In some embodiments, each R⁹ is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofamino, Me, Et, F, Cl, and —CF₃.

In some embodiments, each R¹⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofH, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF3.

In some embodiments, each R¹¹is one substituent attached to the aryl andis independently selected from the group consisting of H, —(C₁₋₄ alkyl),halide, —CF₃, and —CN.

In some embodiments, each R¹¹is one substituent attached to the aryl andis independently selected from the group consisting of —(C₁₋₄ alkyl),halide, —CF₃, and —CN.

In some embodiments, each R¹¹is one substituent attached to the aryl andis independently selected from the group consisting of Me, Et, F, Cl,and —CF₃.

In some embodiments, each R¹² is independently selected from the groupconsisting of —(C₁₋₉ alkyl), —heteroaryl(R¹⁸)_(q), —aryl(R¹⁹)_(k),—CH₂aryl(R¹⁹)_(k), —carbocyclyl(R²⁰)_(j), and —CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, each R¹² is independently selected from the groupconsisting of —(C₁₋₉ alkyl), —heteroaryl(R¹⁸)_(q), —aryl(R¹⁹)_(k),—CH₂aryl(R¹⁹)_(k), —carbocyclyl(R²⁰)_(j), —CH₂carbocyclyl(R²⁰)_(j),—(C₁₋₄ alkylene)_(p)NR²³R²⁴, —heterocyclyl(R²¹)_(h), and—CH₂heterocyclyl(R²¹)_(h).

In some embodiments, each R¹² is independently selected from the groupconsisting of —(C₁₋₅ alkyl), —phenyl(R¹⁹)_(k), —(CH₂)phenyl(R¹⁹)_(k),—carbocyclyl(R²⁰)_(j), —(CH₂)carbocyclyl(R²⁰)_(j), —(CH₂)N(C₁₋₃ alkyl)₂,and —(CH₂)heterocyclyl(R²¹)_(h).

In some embodiments, each R¹³ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R¹³ is independently selected from the groupconsisting of H and —(C₁₋₃ alkyl).

In some embodiments, each R¹⁴ is independently selected from the groupconsisting of H, —(C₁₋₆ alkyl), —CH₂aryl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, each R¹⁴ is independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, each R¹⁵ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R¹⁵ is independently selected from the groupconsisting of H and —(C₁₋₃ alkyl).

In some embodiments, each R¹⁶ is independently selected from the groupconsisting of H, —(C₁₋₆ alkyl), —CH₂aryl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, each R¹⁶ is independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, each R¹⁷ is independently a —(C₁₋₆ alkyl).

In some embodiments, each R¹⁷ is independently a —(C₁₋₃ alkyl).

In some embodiments, each R¹⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting of H,—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF3.

In some embodiments, each R¹⁹ is one substituent attached to the aryland is independently selected from the group consisting of H, —(C₁₋₄alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁹ is one substituent attached to the aryland is independently selected from the group consisting of —(C₁₋₄alkyl), halide, —CF₃, and —CN.

In some embodiments, each R¹⁹ is one substituent attached to the aryland is independently selected from the group consisting of Me, Et, F,Cl, and —CF₃.

In some embodiments, each R²⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofH, —(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²⁰ is one substituent attached to thecarbocyclyl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF₃.

In some embodiments, each R²¹is one substituent attached to theheterocyclyl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN.

In some embodiments, each R²¹is one substituent attached to theheterocyclyl and is independently selected from the group consisting ofMe, Et, F, Cl, and —CF₃.

In some embodiments, R²² is selected from the group consisting of H,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²¹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R²⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹⁹)_(k),and —(C₁₋₆ alkylene)_(p)NR²³R²⁴.

In some embodiments, R²² is selected from the group consisting of H,—Me, —Et, —iPr, —heterocyclyl(R²¹)_(h), —(CH₂CH₂)heterocyclyl(R²¹)_(h),—carbocyclyl(R²⁰)_(j), —(CH₂)phenyl(R¹⁹)_(k), and —(CH₂CH₂)N(C₁₋₃alkyl)₂.

In some embodiments, each R²³ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R²³ is independently selected from the groupconsisting of Me and Et.

In some embodiments, each R²⁴ is independently selected from the groupconsisting of H and —(C₁₋₆ alkyl).

In some embodiments, each R²⁴ is independently selected from the groupconsisting of Me and Et.

In some embodiments, R²⁵ is selected from the group consisting of H,—(C₁₋₆ alkyl), —(C₁₋₄ alkylene)_(p)heterocyclyl(R²¹)_(h), and —(C₁₋₆alkylene)_(p)NR²³R²⁴.

In some embodiments, R²⁵ is selected from the group consisting of H,—Me, —Et, —iPr, —(CH₂CH₂)heterocyclyl(R²¹)_(h), and —(CH₂CH₂)N(C₁₋₃alkyl)₂.

In some embodiments, each p is independently 0 or 1.

In some embodiments, each q is independently 1to 4.

In some embodiments, each h is independently 1to 10.

In some embodiments, each k is independently 1to 5.

In some embodiments, each j is independently 1to 12.

In some embodiments, each p is independently 0 or 1; in someembodiments, each p is 0; in some embodiments, each p is 1.

In some embodiments, each q is independently 0 to 4; in someembodiments, each q is 0; in some embodiments, each q is 1; in someembodiments, each q is 2; in some embodiments, each q is 3; in someembodiments, each q is 4.

In some embodiments, each h is independently 0 to 10; in someembodiments, each h is 0; in some embodiments, each h is 1; in someembodiments, each h is 2; in some embodiments, each h is 3; in someembodiments, each h is 4.

In some embodiments, each k is independently 0 to 5; in someembodiments, each k is 0; in some embodiments, each k is 1; in someembodiments, each k is 2; in some embodiments, each k is 3.

In some embodiments, each j is independently 0 to 12; in someembodiments, each j is 0; in some embodiments, each j is 1; in someembodiments, each j is 2; in some embodiments, each j is 3; in someembodiments, each j is 4.

In some embodiments, each R⁴ is one substituent attached to theheteroaryl and is selected from the group consisting of —(C₁₋₃ alkyl),—CH₂heterocyclyl(R⁹)_(h), —NHC(═O)R¹², —NR¹³R¹⁴, and —CH₂NR¹⁵R¹⁶.

In some embodiments, at least one R⁹ is halide.

In some embodiments, R¹² is selected from the group consisting of —(C₁₋₅alkyl), —phenyl(R¹⁹)_(k), —CH₂phenyl(R¹⁹)_(k), and—carbocyclyl(R²⁰)_(j).

In some embodiments, R¹³ and R¹⁴ are independently selected from H and—(C₁₋₅ alkyl).

In some embodiments, R¹⁵ and R¹⁶ are independently selected from H and—(C₁₋₅ alkyl).

In some embodiments, k is 1or 2 and each R⁸ is independently a halide.

In some embodiments, k is 2, one R⁸ is halide and the other R⁸ is—CH₂NHSO₂R¹⁷.

In some embodiments, R¹⁷ is —(C₁₋₃ alkyl).

In some embodiments, k is 2, one R⁸ is halide and the other R⁸ is—NHCH₂CH₂NR¹³R¹⁴.

In some embodiments, R¹³ and R¹⁴ are independently selected from H and—(C₁₋₃ alkyl).

In some embodiments, R³ is selected from the group consisting of—pyridinyl(R⁶)_(q), —imidazolyl(R⁶)_(q), —furanyl(R⁶)_(q), and—thiophenyl(R⁶)_(q).

In some embodiments, q is 0 or 1, R⁶ is selected from the groupconsisting of halide, —(C₁₋₃ alkyl), —C(═O)R¹⁷, and R¹⁷ is —(C₁₋₂alkyl).

In some embodiments, R³ is selected from the group consisting of—piperidinyl(R⁷)_(h) and —piperazinyl(R⁷)_(h).

In some embodiments, q is 1, and R⁷ is selected from the groupconsisting of H and —(C₁₋₃ alkyl).

In some embodiments, R² is H; in other embodiments, R² is halide, e.g.F.

In some embodiments, R¹is —heteroaryl(R⁴)_(q).

In some embodiments, R¹is —pyridinyl(R⁴)_(q).

In some embodiments, R¹is —pyridin-3-yl(R⁴)_(q).

In some embodiments, R¹is —pyrimidinyl(R⁴)_(q).

In some embodiments, R¹is —pyrimidin-5-yl(R⁴)_(q).

In some embodiments, R¹is —pyrimidin-5-yl(R⁴)_(q) and q is 0.

In some embodiments, R¹is —pyrazinyl(R⁴)_(q).

In some embodiments, R¹is —pyrazolyl(R⁴)_(q).

In some embodiments, R¹is —pyrazol-4-yl(R⁴)_(q), q is 1, and R⁴ is Me.

In some embodiments, R¹is —pyrazol-4-yl(R⁴)_(q) and q is 0.

In some embodiments, R¹is —imidazolyl(R⁴)_(q).

In some embodiments, R¹is —imidazol-5-yl(R⁴)_(q), q is 1, and R⁴ is Me.

In some embodiments, R¹is —imidazol-5-yl(R⁴)_(q), q is 2, and both R⁴are Me.

In some embodiments, R¹is —heterocyclyl(R⁵)_(h).

In some embodiments, R¹is —piperidinyl(R⁵)_(h).

In some embodiments, R¹is —piperidin-4-yl(R⁵)_(h).

In some embodiments, R¹is —piperidin-4-yl(R⁵)_(h), and h is 0.

In some embodiments, R¹is —tetrahydropyridinyl(R⁵)_(h).

In some embodiments, R¹is —1,2,3,6-tetrahydropyridinyl(R⁵)_(h).

In some embodiments, R¹is —1,2,3,6-tetrahydropyridinyl(R⁵)_(h), and h is0.

In some embodiments, R³ is —heteroaryl(R⁶)_(q).

In some embodiments, R³ is —heterocyclyl(R⁷)_(h).

In some embodiments, R³ is —piperidinyl(R⁷)_(h).

In some embodiments, R³ is —piperazinyl(R⁷)_(h).

In some embodiments, R³ is —aryl(R⁸)_(k).

In some embodiments, R³ is —pyridinyl(R⁶)_(q).

In some embodiments, R³ is —pyridin-3-yl(R⁶)_(q).

In some embodiments, R³ is —pyridin-4-yl(R⁶)_(q).

In some embodiments, R³ is —pyridin-5-yl(R⁶)_(q).

In some embodiments, R³ is —pyridin-3-yl(R⁶)_(q), q is 0.

In some embodiments, R³ is —pyridin-4-yl(R⁶)_(q), q is 0.

In some embodiments, R³ is —pyridin-5-yl(R⁶)_(q), q is 0.

In some embodiments, R³ is —imidazolyl(R⁶)_(q).

In some embodiments, R³ is —imidazol-1-yl(R⁶)_(q), q is 1, and R⁶ is—(C₁₋₃ alkyl).

In some embodiments, R³ is —imidazol-1-yl(R⁶)_(q), q is 1, and R⁶ ismethyl.

In some embodiments, R³ is —furanyl(R⁶)_(q).

In some embodiments, R³ is —furan-2-yl(R⁶)_(q).

In some embodiments, R³ is —furan-2-yl(R⁶)_(q) and q is 0.

In some embodiments, R³ is —furan-3-yl(R⁶)_(q).

In some embodiments, R³ is —furan-3-yl(R⁶)_(q) and q is 0.

In some embodiments, R³ is —thiophenyl(R⁶)_(q).

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q).

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q) and q is 0.

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1or 2, and eachR⁶ is independently a halide.

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1or 2, and R⁶ isF.

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1or 2, and eachR⁶ is independently —(C₁₋₆ alkyl).

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1or 2, and eachR⁶ is independently —(C₁₋₂ alkyl).

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1or 2, and R⁶ ismethyl.

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1or 2, and R⁶ is—CF₃.

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1or 2, and R⁶ isCN.

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1, and R⁶ is—C(═O)R¹⁷.

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is —(C₁₋₆ alkyl).

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is —(C₁₋₄ alkyl).

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is —(C₁₋₂ alkyl).

In some embodiments, R³ is —thiophen-2-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q).

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q) and q is 0.

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q), q is 1or 2, and eachR⁶ is independently halide.

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q), q is 1or 2, and R⁶ isF.

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q), q is 1or 2, and eachR⁶ is independently —(C₁₋₆ alkyl).

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q), q is 1or 2, and eachR⁶ is independently —(C₁₋₂alkyl).

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q), q is 1or 2, and R⁶ ismethyl.

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q), q is 1or 2, and R⁶ is—CF₃.

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q), q is 1or 2, and R⁶ isCN.

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q), q is 1, and R⁶ is—C(═O)R¹⁷.

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is —(C₁₋₄ alkyl).

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is —(C₁₋ ₂alkyl).

In some embodiments, R³ is —thiophen-3-yl(R⁶)_(q), q is 1, R⁶ is—C(═O)R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is selected from the group consisting of:

In some embodiments, R³ is —phenyl(R⁸)k.

In some embodiments, R³ is —phenyl(R⁸)_(k) and k is 0.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 1or 2, and each R⁸ isindependently a halide.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 1or 2, and R⁸ is F.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 1, and R⁸ is F.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —(C₁₋₆ alkylene)_(p)NHSO₂R¹⁷.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —(C₁₋₄ alkylene)_(p)NHSO₂R¹⁷, and p is 1.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —(C₁₋₂alkylene)_(p)NHSO₂R¹⁷, and p is 1.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is -CH₂NHSO₂R¹⁷.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is —(C₁₋₄ alkyl).

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is —(C₁₋₂ alkyl).

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is a halideand the other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is —(C₁₋₂ alkyl).

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NR13(C₁₋₆alkylene)NR¹³R¹⁴.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NR13(C₁₋₅alkylene)NR¹³R¹⁴.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NR13(C₁₋₄alkylene)NR¹³R¹⁴.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NR13(C₁₋₃alkylene)NR¹³R¹⁴.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NR13CH₂CH₂NR¹³R¹⁴.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, R⁸ is halide and theother R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are independently selectedfrom —(C₁₋₆ alkyl).

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are independentlyselected from —(C₁₋₄ alkyl).

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are independentlyselected from —(C₁₋₂ alkyl).

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are both methyl.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are independently selectedfrom —(C₁₋₂ alkyl).

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —NHCH₂CH₂NR¹³R¹⁴, and R¹³ and R¹⁴ are both methyl.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —OCH₂CH₂NR²³R²⁴.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —OCH₂CH₂NR²³R²⁴, and R²³ and R²⁴ are independently a—(C₁₋₂ alkyl).

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —OCH₂CH₂NR²³R²⁴, and R²³ and R²⁴ are both methyl.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —OCH₂CH₂NR²³R²⁴, and R²³ and R²⁴ are both methyl.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is —(C₁₋₄ alkyl).

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is —(C₁₋₂ alkyl).

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is halide andthe other R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —CH₂NHSO2R¹⁷, and R¹⁷ is —(C₁₋₂ alkyl).

In some embodiments, R³ is —phenyl(R⁸)_(k), k is 2, one R⁸ is F and theother R⁸ is —CH₂NHSO₂R¹⁷, and R¹⁷ is methyl.

In some embodiments, R³ is selected from the group consisting of:

In some embodiments, R³ is —piperidinyl(R⁷)_(h).

In some embodiments, R³ is —piperidin-1-yl(R⁷)_(h).

In some embodiments, R³ is —piperidin-1-yl(R⁷)_(h) and h is 0.

In some embodiments, R³ is —piperidin-1-yl(R⁷)_(h), h is 1or 2, and eachR⁷ is independently selected from a halide.

In some embodiments, R³ is —piperazinyl(R⁷)_(h).

In some embodiments, R³ is —piperazin-1-yl(R⁷)_(h).

In some embodiments, R³ is —piperazin-1-yl(R⁷)_(h), h is 1, and R⁷ isC₁₋₃ alkyl.

In some embodiments, R³ is —piperazin-1-yl(R⁷)_(h), h is 1, and R⁷ ismethyl.

In some embodiments, R³ is —morpholinyl(R⁷)_(h).

In some embodiments, R³ is —morpholin-1-yl(R⁷)_(h).

In some embodiments, R³ is —morpholin-1-yl(R⁷)_(h) and h is 0.

In some embodiments, R³ is selected from the group consisting of:

In some embodiments, q is 0.

In some embodiments, at least one R⁴ is a halide.

In some embodiments, at least one R⁴ is a F.

In some embodiments, R⁴ is F.

In some embodiments, at least one R⁴ is —(C₁₋₆ alkyl).

In some embodiments, at least one R⁴ is —(C₁₋₅ alkyl).

In some embodiments, at least one R⁴ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁴ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁴ is —(C₁₋₂ alkyl).

In some embodiments, R⁴ is a methyl.

In some embodiments, at least one R⁴ is —(C₁₋₄alkylene)_(p)heterocyclyl(R⁹)_(h) and p is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₃alkylene)_(p)heterocyclyl(R⁹)_(h) and p is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₂alkylene)_(p)heterocyclyl(R⁹)_(h) and p is 0 or 1.

In some embodiments, at least one R⁴ is —CH₂pyrrolidinyl(R⁹)_(h).

In some embodiments, at least one R⁴ is —CH₂pyrrolidinyl(R⁹)_(h)and h is0.

In some embodiments, R⁴ is a —CH₂pyrrolidinyl(R⁹)_(h)and h is 0.

In some embodiments, at least one R⁴ is —CH₂pyrrolidinyl(R⁹)_(h), h is1or 2, and at least one R⁹ is halide.

In some embodiments, at least one R⁴ is —CH₂pyrrolidinyl(R⁹)_(h), h is1or 2, and at least one R⁹ is F.

In some embodiments, R⁴ is a —CH₂pyrrolidinyl(R⁹)_(h), h is 1or 2, andat least one R⁹ is halide.

In some embodiments, R⁴ is —CH₂pyrrolidinyl(R⁹)_(h), h is 1or 2, and atleast one R⁹ is F.

In some embodiments, R⁶ is a —CH₂pyrrolidinyl(R⁹)_(h), h is 1or 2, andeach R⁹ is F.

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h).

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h)and h is0.

In some embodiments, R⁴ is a —CH₂piperidinyl(R⁹)_(h) and h is 0.

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h) and atleast one R⁹ is halide.

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h) and atleast one R⁹ is F.

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h), h is1or 2, and at least one R⁹ is halide.

In some embodiments, at least one R⁴ is —CH₂piperidinyl(R⁹)_(h), h is1or 2, and at least one R⁹ is F.

In some embodiments, R⁴ is —CH₂piperidinyl(R⁹)_(h), h is 1or 2, and eachR⁹ is a halide.

In some embodiments, R⁴ is —CH₂piperidinyl(R⁹)_(h), h is 1or 2, and eachR⁹ is F.

In some embodiments, R⁴ is a —CH₂piperidinyl(R⁹)_(h), h is 1or 2, andeach R⁹ is F.

In some embodiments, R⁴ is a

In some embodiments, at least one R⁴ is —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j).

In some embodiments, at least one R⁴ is —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j) and j is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₃alkylene)_(p)carbocyclyl(R¹⁰)_(j) and j is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₂alkylene)_(p)carbocyclyl(R¹⁰)_(j) and j is 0 or 1.

In some embodiments, at least one R⁴ is —CH₂carbocyclyl(R¹⁰)_(j).

In some embodiments, R⁴ is a —CH₂carbocyclyl(R¹⁰)_(j).

In some embodiments, at least one R⁴ is —(C₁₋₄alkylene)_(p)aryl(R¹¹)_(k) and k is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₃alkylene)_(p)aryl(R¹¹)_(k) and k is 0 or 1.

In some embodiments, at least one R⁴ is —(C₁₋₂alkylene)_(p)aryl(R¹¹)_(k) and k is 0 or 1.

In some embodiments, at least one R⁴ is —CH₂aryl(R¹¹)_(k).

In some embodiments, at least one R⁴ is —CH₂phenyl(R¹¹)_(k).

In some embodiments, R⁴ is a —CH₂phenyl(R¹¹)_(k).

In some embodiments, at least one R⁴ is —NHC(═O)R¹².

In some embodiments, R⁴ is a —NHC(═O)R¹².

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₉alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₈alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₇alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₆alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₅alkyl).

In some embodiments, R⁴ is a —NHC(═O)R¹² and R¹² is —(C₁₋₅ alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₄alkyl).

In some embodiments, R⁴ is a —NHC(═O)R¹² and R¹² is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₃alkyl).

In some embodiments, R⁴ is a —NHC(═O)R¹² and R¹² is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₁₋₂alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₂₋₅alkyl).

In some embodiments, R⁴ is a —NHC(═O)R¹² and R¹² is —(C₂₋₅ alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is —(C₃₋₄alkyl).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is—aryl(R¹⁹)_(k).

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is—phenyl(R¹⁹)_(k), and k is 0.

In some embodiments, R⁴ is a —NHC(═O)R¹², R¹² is —phenyl(R¹⁹)_(k), and kis 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is—CH₂aryl(R¹⁹)_(k).

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is—CH₂phenyl(R¹⁹)_(k), and k is 0.

In some embodiments, R⁴ is —NHC(═O)R¹², R¹² is —CH₂phenyl(R¹⁹)_(k), andk is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is—heteroaryl(R¹⁸)_(q).

In some embodiments, at least one R⁴ is —NHC(═O)R¹² and R¹² is—carbocyclyl(R²⁰)_(j).

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is—carbocyclyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is—cyclopropyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHC(═O)R^(12,) R¹² is—cyclopropyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R¹², R¹² is—cyclobutyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHC(═O)R^(12,) R¹² is—cyclobutyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R^(12,) R¹²—cyclopentyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHC(═O)R^(12,) R¹² is—cyclopentyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R^(12,) R¹² is—cyclohexyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHC(═O)R^(12,) R¹² is—cyclohexyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R^(12,) R¹² is—CH₂carbocyclyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —NHC(═O)R^(12,) R¹² is—CH₂cyclopropyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —NR¹³R¹⁴.

In some embodiments, at least one R⁴ is NR¹³R¹⁴, R¹³ and R¹⁴ areindependently selected from the group consisting of H and —(C₁₋₆ alkyl).

In some embodiments, at least one R⁴ is NR¹³R¹⁴, and R¹³ and R¹⁴ areindependently selected from the group consisting of H and —(C₁₋₅ alkyl).

In some embodiments, at least one R⁴ is NR¹³R¹⁴, and R¹³ and R¹⁴ areindependently selected from the group consisting of H and —(C₁₋₄ alkyl).

In some embodiments, at least one R⁴ is NR¹³R¹⁴, and R¹³ and R¹⁴ areindependently selected from the group consisting of H and —(C₁₋₃ alkyl).

In some embodiments, at least one R⁴ is NR¹³R¹⁴, and R¹³ and R¹⁴ areindependently selected from the group consisting of H and —(C₁₋₂ alkyl).

In some embodiments, at least one R⁴ is NR¹³R¹⁴, and R¹³ and R¹⁴ areindependently selected from the group consisting of H and methyl.

In some embodiments, at least one R⁴ is —NH₂.

In some embodiments, R⁴ is a —NH₂.

In some embodiments, at least one R⁴ is —NHR¹⁴ and R¹⁴ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁴ is —NHR¹⁴ and R¹⁴ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁴ is —NHR¹⁴ and R¹⁴ is —(C₁₋₂ alkyl).

In some embodiments, R⁴ is a —NHR¹⁴ and R¹⁴ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁴ is —NHR¹⁴ and R¹⁴ is—CH₂aryl(R¹⁹)_(k).

In some embodiments, at least one R⁴ is —NHR¹⁴, R¹⁴ is—CH₂phenyl(R¹⁹)_(k), and k is 0.

In some embodiments, R⁴ is —NHR¹⁴, R¹⁴ is —CH₂phenyl(R¹⁹)_(k), and k is0.

In some embodiments, at least one R⁴ is —NHR¹⁴ and R¹⁴ is—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, at least one R⁴ is —NHR¹⁴, R¹⁴ is—CH₂cyclopropyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHR¹⁴, R¹⁴ is —CH₂cyclopropyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —NHR¹⁴, R¹⁴ is—CH₂cyclobutyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHR¹⁴, R¹⁴ is —CH₂cyclobutyl(R²⁰)_(j), andj is 0.

In some embodiments, at least one R⁴ is —NHR¹⁴, R¹⁴ is—CH₂cyclopentyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHR^(14,) R¹⁴ is —CH₂cyclopentyl(R²⁰)_(j),and j is 0.

In some embodiments, at least one R⁴ is —NHR¹⁴ R¹⁴, is—CH₂cyclohexyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —NHR¹⁴, R¹⁴ is —CH₂cyclohexyl(R²⁰)_(j), andj is 0.

In some embodiments, at least one R⁴ is —(C₁₋₆ alkylene)NR¹⁵R¹⁶.

In some embodiments, at least one R⁴ is —(C₁₋₅ alkylene)NR¹⁵R¹⁶.

In some embodiments, at least one R⁴ is —(C₁₋₄ alkylene)NR¹⁵R¹⁶.

In some embodiments, at least one R⁴ is —(C₁₋₃ alkylene)NR¹⁵R¹⁶.

In some embodiments, at least one R⁴ is —(C₁₋₂alkylene)NR¹⁵R¹⁶.

In some embodiments, at least one R⁴ is —CH₂NR¹⁵R¹⁶.

In some embodiments, R⁴ is a —CH₂NR¹⁵R¹⁶.

In some embodiments, at least one R₄ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₆ alkyl).

In some embodiments, at least one R₄ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₅ alkyl).

In some embodiments, at least one R₄ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₄ alkyl).

In some embodiments, at least one R₄ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₃ alkyl).

In some embodiments, at least one R₄ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and —(C₁₋₂ alkyl).

In some embodiments, at least one R₄ is —CH₂NR¹⁵R¹⁶, and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and methyl.

In some embodiments, R⁴ is a —CH₂NR¹⁵R¹⁶and R¹⁵ and R¹⁶ areindependently selected from the group consisting of H and methyl.

In some embodiments, at least one R⁴ is —CH₂NH₂.

In some embodiments, R⁴ is a —CH₂NH₂.

In some embodiments, at least one R⁴ is —CH₂NMe₂.

In some embodiments, R⁴ is —CH₂NMe₂.

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶ and R¹⁶ is —(C₁₋₄alkyl).

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶ and R¹⁶ is —(C₁₋₃alkyl).

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶ and R¹⁶ is —(C₁₋₂alkyl).

In some embodiments, R⁴ is a —CH₂NHR¹⁶ and R¹⁶ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶ and R¹⁶ is—CH₂aryl(R¹⁹)_(k).

In some embodiments, at least one R⁴ is —CH₂NHR^(16,) R¹⁶ is—CH₂phenyl(R¹⁹)_(k), and k is 0.

In some embodiments, R⁴ is a —CH₂NHR^(16,) R¹⁶ is —CH₂phenyl(R¹⁹)_(k),and k is 0.

In some embodiments, at least one R⁴ is —CH₂NHR¹⁶ and R¹⁶ is—CH₂carbocyclyl(R²⁰)_(j).

In some embodiments, at least one R⁴ is —CH₂NHR^(16,) R¹⁶ is—CH₂cyclopropyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —CH₂NHR^(16,) R¹⁶ is—CH₂cyclopropyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —CH₂NHR^(16,) R¹⁶ is—CH₂cyclobutyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —CH₂NHR^(16,) R¹⁶ is—CH₂cyclobutyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —CH₂NHR^(16,) R¹⁶ is—CH₂cyclopentyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —CH₂NHR^(16,) R¹⁶ is—CH₂cyclopentyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —CH₂NHR^(16,) R¹⁶ is—CH₂cyclohexyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —CH₂NHR^(16,) R¹⁶ is—CH₂cyclohexyl(R²⁰)_(j), and j is 0.

In some embodiments, at least one R⁴ is —OR²².

In some embodiments, at least one R⁴ is —OH.

In some embodiments, R⁴ is a —OH.

In some embodiments, at least one R⁴ is —OR²² and R²² is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁴ is —OR²² and R²² is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁴ is —OMe.

In some embodiments, R⁴ is a —OMe.

In some embodiments, at least one R⁴ is —OR²², R²² is—heterocyclyl(R²¹)_(h), and h is 0.

In some embodiments, R⁴ is a —OR²², R²² is —heterocyclyl(R²¹)_(h), and his 0.

In some embodiments, at least one R⁴ is —OR²², R²² is—carbocyclyl(R²⁰)_(j), and j is 0.

In some embodiments, R⁴ is a —OR²², R²² is —carbocyclyl(R²⁰)_(j), and jis 0.

In some embodiments, at least one R⁴ is —OR^(22,) R²² is —(C₁₋₄alkylene)heterocyclyl(R²¹)_(h), and h is 0.

In some embodiments, at least one R⁴ is —OR^(22,) R²² is—(CH₂CH₂)heterocyclyl(R²¹)_(h), and h is 0.

In some embodiments, R⁴ is a —OR²², R²² is—(CH₂CH₂)heterocyclyl(R²¹)_(h), and h is 0.

In some embodiments, at least one R⁴ is —OR²², R²² is —(C₁₋₄alkylene)NR²³R²⁴ and R²³ and R²⁴ are independently a —(C₁₋₄ alkyl).

In some embodiments, at least one R⁴ is —OR²², R²² is —(CH₂CH₂)NR²³R²⁴R²³ and R²⁴ are independently a —(C₁₋₂ alkyl).

In some embodiments, at least one R⁴ is —OR²², and R²² is —(CH₂CH₂)NMe₂.

In some embodiments, R⁴ is a —OR²², R²² is —(CH₂CH₂)NMe₂.

In some embodiments, at least one R⁴ is —OR²², R²² is —(C₁₋₄alkylene)aryl(R¹⁹)_(k), k is 0 or 1and R¹⁹ is halide.

In some embodiments, at least one R⁴ is —OR²², R²² is—(CH₂CH₂)phenyl(R¹⁹)_(k), k is 0 or 1and R¹⁹ is a halide.

In some embodiments, R⁴ is a —OR²², R²² is —(CH₂CH₂)phenyl(R¹⁹)_(k), kis 0 or 1and R¹⁹ is a halide.

In some embodiments, at least one R⁴ is —OR²², R²² is—(CH₂)phenyl(R¹⁹)_(k), k is 0 or 1and R¹⁹ is a halide.

In some embodiments, R⁴ is a —OR²², R²² is —(CH₂)phenyl(R¹⁹)_(k), k is 0or 1and R¹⁹ is a halide.

In some embodiments, h is 0.

In some embodiments, at least one R⁵ is a halide.

In some embodiments, at least one R⁵ is a F.

In some embodiments, at least one R⁵ is —(C₁₋₆ alkyl).

In some embodiments, at least one R⁵ is —(C₁₋₅ alkyl).

In some embodiments, at least one R⁵ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁵ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁵ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁵ is methyl.

In some embodiments, at least one R⁶ is a halide.

In some embodiments, at least one R⁶ is a F.

In some embodiments, at least one R⁶ is —(C₁₋₄ alkyl).

In some embodiments, at least one R⁶ is —(C₁₋₃ alkyl).

In some embodiments, at least one R⁶ is —(C₁₋₂ alkyl).

In some embodiments, at least one R⁶ is methyl.

In some embodiments, R⁶ is a methyl.

In some embodiments, at least one R⁶ is —C(═O)(C₁₋₃ alkyl).

In some embodiments, at least one R⁶ is —C(═O)Me.

In some embodiments, R⁶ is a —C(═O)Me.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R^(12;) R¹² is —(C₂₋₅ alkyl); R³ is —phenyl(R⁸)_(k); k is 1or 2;and R⁸ is F.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is —phenyl(R⁸)_(k); k is 2; one R⁸is F and the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁷; p is 1; and R¹⁷is —(C₁₋₃ alkyl).

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R^(12;) R¹² is —(C₂₋₅ alkyl); R³ is —phenyl(R⁸)_(k); k is 2; oneR⁸ is F and the other R⁸ is —NH(C₁₋₆ alkylene)NR¹³R¹⁴; and R¹³ and R¹⁴are independently selected from —(C₁₋₃ alkyl).

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is —heteroaryl(R⁶)_(q),wherein q is 1; R⁶ is selected from the group consisting of halide,—(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃ alkyl); and the heteroarylis selected from the group consisting of pyridine, furan, thiophene, andimidazole.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is —heterocyclyl(R⁷)_(h); h is 1or2; and R⁷ is selected from the group consisting of halide and —(C₁₋₂alkyl).

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —carbocyclyl(R²⁰)_(j); j is 0; R³ is—phenyl(R⁸)_(k); k is 1or 2; R⁸ is F; and the carbocyclyl is selectedfrom the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —carbocyclyl(R²⁰)_(j); j is 0; R³ is—phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —(C₁₋₂alkylene)_(p)NHSO₂R¹⁷; p is 1; R¹⁷ is —(C₁₋₃ alkyl); and the carbocyclylis selected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —carbocyclyl(R²⁰)_(k); j is 0; R³ is—phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —NH(C₁₋₆alkylene)NR¹³R¹⁴; R¹³ and R¹⁴ are independently selected from —(C₁₋₃alkyl); and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —NHC(═O)R¹²; R¹² is —carbocyclyl(R²⁰)_(j); j is 0; R³ is—heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is C₁₋₃ alkyl;the heteroaryl is selected from the group consisting of pyridine, furan,thiophene, and imidazole; and the carbocyclyl is selected from the groupconsisting of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —carbocyclyl(R²⁰)_(j); j is 0; R³ is—heterocyclyl(R⁷)_(h); h is 1or 2; R⁷ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl); and the carbocyclyl is selectedfrom the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶ R¹³ andR¹⁵ are independently selected from the group consisting of H and —(C₁₋₃alkyl); R¹⁴ and R¹⁶ are independently selected from the group consistingof H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j),wherein j and k are 0; R³ is —phenyl(R⁸)_(k), wherein k is 1or 2; R⁸ isF; and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵ _(R) ¹⁶ _(;)R¹³ and R¹⁵ are independently selected from the group consisting of Hand —(C₁₋₃ alkyl); R¹⁴ and R¹⁶ are independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j), wherein j and k are 0; R³ is —phenyl(R⁸)_(k),wherein k is 2; one R⁸ is F and the other R⁸ is —(C₁₋₂alkylene)_(p)NHSO2R¹⁷; p is 1; R¹⁷ is —(C₁₋₃ alkyl); and the carbocyclylis selected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R^(16,)wherein R¹³ and R¹⁵ are independently selected from the group consistingof H and —(C₁₋₃ alkyl), and R¹⁴ and R¹⁶ are independently selected fromthe group consisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j), wherein k and j are 0; R³ is —phenyl(R⁸)_(k),wherein k is 2; one R⁸ is F and the other R⁸ is —NH(C₁₋₆alkylene)NR¹³R¹⁴, wherein R¹³ and R¹⁴ are independently selected from—(C₁₋₃ alkyl); and the carbocyclyl is selected from the group consistingof cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is selected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶;R¹³ and R¹⁵ are independently selected from the group consisting of Hand —(C₁₋₃ alkyl); R¹⁴ and R¹⁶ are independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j); k and j are 0; R³ is —heteroaryl(R⁶)_(q),wherein q is 1; R⁶ is selected from the group consisting of halide,—(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃ alkyl); the heteroaryl isselected from the group consisting of pyridine, furan, thiophene, andimidazole; and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶; R¹³ andR¹⁵ are independently selected from the group consisting of H and —(C₁₋₃alkyl); R¹⁴ and R¹⁶ are independently selected from the group consistingof H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j);k and j are 0; R³ is —heterocyclyl(R⁷)_(h); h is 1or 2; R⁷ is selectedfrom the group consisting of halide and —(C₁₋₂ alkyl); and thecarbocyclyl is selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is —phenyl(R⁸)_(k); k is1or 2; R⁸ is F; and the heterocyclyl is selected from the groupconsisting of pyrrolidine and piperidine.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is —phenyl(R⁸)_(k); k is2; one R⁸ is F and the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO2R¹⁷; p is 1;R¹⁷ is —(C₁₋₃ alkyl); and the heterocyclyl is selected from the groupconsisting of pyrrolidine and piperidine.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is —phenyl(R⁸)_(k); k is2; and R⁸ is one F and the other R⁸ —NH(C₁₋₆ alkylene)NR¹³R¹⁴; R¹³ andR¹⁴ are independently selected from —(C₁₋₃ alkyl); and the heterocyclylis selected from the group consisting of pyrrolidine and piperidine.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is—heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃alkyl); the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole; and the heterocyclyl isselected from the group consisting of pyrrolidine and piperidine.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h), wherein h is 0-2; R⁹ is F; R³ is—heterocyclyl(R⁷)_(h), wherein h is 1or 2; R⁷ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl); and the heterocyclyl is selectedfrom the group consisting of pyrrolidine and piperidine.

In some embodiments, R² is H; R¹is —pyrimidinyl(R⁴)_(q); q is 0; R³ is—phenyl(R⁸)_(k); k is 1or 2; and R⁸ is F.

In some embodiments, R² is H; R¹is —pyrimidinyl(R⁴)_(q); q is 0; R³ is—phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is—(C₁₋₂alkylene)_(p)NHSO2R¹⁷; p is 1; and R¹⁷ is —(C₁₋₃ alkyl).

In some embodiments, R² is H; R¹is —pyrimidinyl(R⁴)_(q); q is 0; R³ is—phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is—NH(C₁₋₆alkylene)NR¹³R¹⁴; and R¹³ and R¹⁴ are independently selectedfrom —(C₁₋₃ alkyl).

In some embodiments, R² is H; R¹is —pyrimidinyl(R⁴)_(q), wherein q is 0;R³ is —heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃alkyl); and the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole.

In some embodiments, R² is H; R¹is —pyrimidinyl(R⁴)_(q); q is 0; R³ is—heterocyclyl(R⁷)_(h); h is 1or 2; R⁷ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl).

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is —phenyl(R⁸)_(k); k is 1or 2;and R⁸ is F.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R^(12;) R¹² is (C₂₋₅ alkyl); R³ is —phenyl(R⁸)_(k); k is 2; oneR⁸ is F and the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁷; p is 1; and R⁷is —(C₁₋₃ alkyl).

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q) q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is —phenyl(R⁸)_(k); k is 2; one R⁸is F and the other R⁸ is —NH(C₁₋₆ alkylene)NR¹³R¹⁴; and R¹³ and R¹⁴ areindependently selected from —(C₁₋₃ alkyl).

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is —heteroaryl(R⁶)_(q),wherein q is 1; R⁶ is selected from the group consisting of halide,—(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃ alkyl); and the heteroarylis selected from the group consisting of pyridine, furan, thiophene, andimidazole.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —(C₂₋₅ alkyl); R³ is —heterocyclyl(R⁷)_(h); h is 1or2; and R⁷ is selected from the group consisting of halide and —(C₁₋₂alkyl).

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —carbocyclyl(R²⁰)_(j); j is 0; R³ is—phenyl(R⁸)_(k); k is 1or 2; R⁸ is F; and the carbocyclyl is selectedfrom the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —carbocyclyl(R²⁰)_(j); j is 0; R³ is—phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —(C₁₋₂alkylene)_(p)NHSO2R¹⁷; p is 1; R¹⁷ is —(C₁₋₃ alkyl); and the carbocyclylis selected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —carbocyclyl(R²⁰)_(j); j is 0; R³ is—phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is —NH(C₁₋₆alkylene)NR¹³R¹⁴; R¹³ and R¹⁴ are independently selected from —(C₁₋₃alkyl); and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —NHC(═O)R¹²; R¹² is —carbocyclyl(R²⁰)_(j); j is 0; R³ is—heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is C₁₋₃ alkyl;the heteroaryl is selected from the group consisting of pyridine, furan,thiophene, and imidazole; and the carbocyclyl is selected from the groupconsisting of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—NHC(═O)R¹²; R¹² is —carbocyclyl(R²⁰)_(j); j is 0; R³ is—heterocyclyl(R⁷)_(h); h is 1or 2; R⁷ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl); and the carbocyclyl is selectedfrom the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶ _(; R) ¹³and R¹⁵ are independently selected from the group consisting of H and—(C₁₋₃ alkyl); R¹⁴ and R¹⁶ are independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j), wherein k and j are 0; R³ is —phenyl(R⁸)_(k),wherein k is 1or 2; R⁸ is F; and the carbocyclyl is selected from thegroup consisting of cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶; R¹³ andR¹⁵ are independently selected from the group consisting of H and —(C₁₋₃alkyl); R¹⁴ and R¹⁶ are independently selected from the group consistingof H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j),wherein k and j are 0; R³ is —phenyl(R⁸)_(k), wherein k is 2; one R⁸ isF and the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁷; p is 1; R¹⁷ is—(C₁₋₃ alkyl); and the carbocyclyl is selected from the group consistingof cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R^(16,)wherein R¹³ and R¹⁵ are independently selected from the group consistingof H and —(C₁₋₃ alkyl), and R¹⁴ and R¹⁶ are independently selected fromthe group consisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j), wherein k and j are 0; R³ is —phenyl(R⁸)_(k),wherein k is 2; one R⁸ is F and the other R⁸ is —NH(C₁₋₆alkylene)NR¹³R¹⁴, wherein R¹³ and R¹⁴ are independently selected from—(C₁₋₃ alkyl); and the carbocyclyl is selected from the group consistingof cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is selected from the group consisting of —NR¹³R¹⁴and —CH₂NR¹⁵R¹⁶;R¹³ and R¹⁵ are independently selected from the group consisting of Hand —(C₁₋₃ alkyl); R¹⁴ and R¹⁶ are independently selected from the groupconsisting of H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and—CH₂carbocyclyl(R²⁰)_(j); k and j are 0; R³ is —heteroaryl(R⁶)_(q),wherein q is 1; R⁶ is selected from the group consisting of halide,—(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃ alkyl); the heteroaryl isselected from the group consisting of pyridine, furan, thiophene, andimidazole; and the carbocyclyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ isselected from the group consisting of —NR¹³R¹⁴ and —CH₂NR¹⁵R¹⁶; R¹³ andR¹⁵ are independently selected from the group consisting of H and —(C₁₋₃alkyl); R¹⁴ and R¹⁶ are independently selected from the group consistingof H, —(C₁₋₃ alkyl), —CH₂phenyl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j);k and j are 0; R³ is —heterocyclyl(R⁷)_(h); h is 1or 2; R⁷ is selectedfrom the group consisting of halide and —(C₁₋₂ alkyl); and thecarbocyclyl is selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, and cyclohexyl.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is —phenyl(R⁸)_(k); k is1or 2; R⁸ is F; and the heterocyclyl is selected from the groupconsisting of pyrrolidine and piperidine.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is —phenyl(R⁸)_(k); k is2; one R⁸ is F and the other R⁸ is —(C₁₋₂ alkylene)_(p)NHSO₂R¹⁷; p is 1;R¹⁷ is —(C₁₋₃ alkyl); and the heterocyclyl is selected from the groupconsisting of pyrrolidine and piperidine.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is —phenyl(R⁸)_(k); k is2; and R⁸ is one F and the other R⁸ is —NH(C₁₋₆alkylene)NR¹³R^(14;) R¹³and R¹⁴ are independently selected from —(C₁₋₃ alkyl); and theheterocyclyl is selected from the group consisting of pyrrolidine andpiperidine.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q), wherein q is1; R⁴ is —CH₂heterocyclyl(R⁹)_(h); h is 0-2; R⁹ is F; R³ is—heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃alkyl); the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole; and the heterocyclyl isselected from the group consisting of pyrrolidine and piperidine.

In some embodiments, R² is F; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—CH₂heterocyclyl(R⁹)_(h), wherein h is 0-2; R⁹ is F; R³ is—heterocyclyl(R⁷)_(h), wherein h is 1or 2; R⁷ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl); and the heterocyclyl is selectedfrom the group consisting of pyrrolidine and piperidine.

In some embodiments, R² is F; R¹is —pyrimidinyl(R⁴)_(q); q is 0; R³ is—phenyl(R⁸)_(k); k is 1or 2; and R⁸ is F.

In some embodiments, R² is F; R¹is —pyrimidinyl(R⁴)_(q); q is 0; R³ is—phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is—(C₁₋₂alkylene)_(p)NHSO₂R¹⁷; p is 1; and R¹⁷ is —(C₁₋₃ alkyl).

In some embodiments, R² is F; R¹is —pyrimidinyl(R⁴)_(q); q is 0; R³ is—phenyl(R⁸)_(k); k is 2; one R⁸ is F and the other R⁸ is—NH(C₁₋₆alkylene)NR¹³R^(14;) and R¹³ and R¹⁴ are independently selectedfrom —(C₁₋₃ alkyl).

In some embodiments, R² is F; R¹is —pyrimidinyl(R⁴)_(q), wherein q is 0;R³ is —heteroaryl(R⁶)_(q), wherein q is 1; R⁶ is selected from the groupconsisting of halide, —(C₁₋₂ alkyl), and —C(═O)R¹⁷; R¹⁷ is —(C₁₋₃alkyl); and the heteroaryl is selected from the group consisting ofpyridine, furan, thiophene, and imidazole.

In some embodiments, R² is F; R¹is —pyrimidinyl(R⁴)_(q); q is 0; R³ is—heterocyclyl(R⁷)_(h); h is 1or 2; R⁷ is selected from the groupconsisting of halide and —(C₁₋₂ alkyl).

In some embodiments, R² is H; R¹is —pyrazol-4-yl(R⁴)_(q); q is 0 or 1;R⁴ is —(C₁₋₃ alkyl); R³ is —phenyl(R⁸)_(k); k is 1or 2; and R⁸ is F.

In some embodiments, R² is H; R¹is —imidazol-5-yl(R⁴)_(q); q is 1or 2;each R⁴ is independently selected from —(C₁₋₃ alkyl); R³ is—phenyl(R⁸)_(k); k is 1or 2; and R⁸ is F.

In some embodiments, R² is H; R¹is —pyridin-3-yl(R⁴)_(q); q is 1; R⁴ is—OR²²; R²² is selected from the group consisting of H and —(C₁₋₃ alkyl);R³ is —phenyl(R⁸)_(k); k is 1or 2; and R⁸ is F.

Illustrative compounds of Formula (I) are shown in Table 1.

TABLE 1 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

172

173

174

175

176

177

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

220

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

257

258

259

260

261

262

263

264

265

266

267

268

269

270

271

272

273

274

275

276

277

278

279

280

281

282

283

284

285

286

287

288

289

290

291

292

293

294

295

296

297

298

299

300

301

302

303

304

305

306

307

308

309

310

311

312

313

314

315

316

317

318

319

320

321

322

323

324

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326

327

328

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340

341

342

343

344

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398

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400

401

402

403

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409

410

411

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419

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422

423

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425

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427

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429

430

431

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450

451

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455

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468

469

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473

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477

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531

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541

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619

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621

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623

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626

627

628

629

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631

632

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650

651

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664

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669

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718

719

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722

723

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726

727

728

729

730

731

732

733

734

735

736

737

738

739

740

741

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745

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750

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764

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769

770

771

772

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784

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786

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790

791

792

793

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795

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799

800

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805

806

807

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809

810

811

812

813

814

815

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817

818

819

820

821

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825

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827

828

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830

831

832

833

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838

839

840

841

842

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849

850

851

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870

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930

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961

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988

989

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1000

1001

1002

1003

1004

1005

1006

1007

1008

1009

1010

1011

1012

1013

1014

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1016

1017

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1019

1020

1021

1022

1023

1024

1025

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1038

1039

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1068

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1080

1081

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1095

1096

1097

1098

1099

1100

1101

1102

1103

1104

1105

1106

1107

1108

1109

1110

1111

1112

1113

1114

1115

1116

1117

1118

1119

1120

1121

1122

1123

1124

1125

1126

1127

1128

1129

1130

1131

1132

1133

1134

1135

1136

1137

1138

1139

1140

1141

1142

1143

1144

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1168

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1171

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1173

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1176

1177

1178

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1184

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1186

1187

1188

1189

1190

1191

1192

1193

1194

1195

1196

1197

1198

1199

1200

1201

1202

1203

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1221

1222

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1234

1235

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1400

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1406

Administration and Pharmaceutical Compositions

Some embodiments include pharmaceutical compositions comprising: (a) atherapeutically effective amount of a compound provided herein, or itscorresponding enantiomer, diastereoisomer or tautomer, orpharmaceutically acceptable salt; and (b) a pharmaceutically acceptablecarrier.

The compounds provided herein may also be useful in combination(administered together or sequentially) with other known agents.

Non-limiting examples of diseases which can be treated with acombination of a compound of Formula (I) and other known agents arecolorectal cancer, ovarian cancer, retinitis pigmentosa, maculardegeneration, diabetic retinopathy, idiopathic pulmonaryfibrosis/pulmonary fibrosis, and osteoarthritis.

In some embodiments, colorectal cancer can be treated with a combinationof a compound of Formula (I) and one or more of the following drugs:5-Fluorouracil (5-FU), which can be administered with the vitamin-likedrug leucovorin (also called folinic acid); capecitabine (XELODA®),irinotecan (CAMPOSTAR®), oxaliplatin (ELOXATIN®. Examples ofcombinations of these drugs which could be further combined with acompound of Formula (I) are FOLFOX (5-FU, leucovorin, and oxaliplatin),FOLFIRI (5-FU, leucovorin, and irinotecan), FOLFOXIRI (leucovorin, 5-FU,oxaliplatin, and irinotecan) and CapeOx (Capecitabine and oxaliplatin).For rectal cancer, chemo with 5-FU or capecitabine combined withradiation may be given before surgery (neoadjuvant treatment).

In some embodiments, ovarian cancer can be treated with a combination ofa compound of Formula (I) and one or more of the following drugs:Topotecan, Liposomal doxorubicin (DOXIL®), Gemcitabine (GEMZAR®),Cyclophosphamide (CYTOXAN®), Vinorelbine (NAVELBINE®), Ifosfamide(IFEX®), Etoposide (VP-16), Altretamine (HEXALEN®), Capecitabine(XELODA®), Irinotecan (CPT-11, CAMPTOSAR®), Melphalan, Pemetrexed(ALIMTA®) and Albumin bound paclitaxel (nab-paclitaxel, ABRAXANE®).Examples of combinations of these drugs which could be further combinedwith a compound of Formula (I) are TIP (paclitaxel [Taxol], ifosfamide,and cisplatin), VeIP (vinblastine, ifosfamide, and cisplatin) and VIP(etoposide [VP-16], ifosfamide, and cisplatin).

In some embodiments, a compound of Formula (I) can be used to treatcancer in combination with any of the following methods: (a) Hormonetherapy such as aromatase inhibitors, LHRH [luteinizinghormone-releasing hormone] analogs and inhibitors, and others; (b)Ablation or embolization procedures such as radiofrequency ablation(RFA), ethanol (alcohol) ablation, microwave thermotherapy andcryosurgery (cryotherapy); (c) Chemotherapy using alkylating agents suchas cisplatin and carboplatin, oxaliplatin, mechlorethamine,cyclophosphamide, chlorambucil and ifosfamide; (d) Chemotherapy usinganti-metabolites such as azathioprine and mercaptopurine; (e)Chemotherapy using plant alkaloids and terpenoids such as vincaalkaloids (i.e. Vincristine, Vinblastine, Vinorelbine and Vindesine) andtaxanes; (f) Chemotherapy using podophyllotoxin, etoposide, teniposideand docetaxel; (g) Chemotherapy using topoisomerase inhibitors such asirinotecan, topotecan, amsacrine, etoposide, etoposide phosphate, andteniposide; (h) Chemotherapy using cytotoxic antibiotics such asactinomycin, anthracyclines, doxorubicin, daunorubicin, valrubicin,idarubicin, epirubicin, bleomycin, plicamycin and mitomycin; (i)Chemotherapy using tyrosine-kinase inhibitors such as Imatinib mesylate(GLEEVEC®, also known as STI-571), Gefitinib (Iressa, also known asZD1839), Erlotinib (marketed as TARCEVA®), Bortezomib (VELCADE®),tamoxifen , tofacitinib, crizotinib, Bcl-2 inhibitors (e.g. obatoclax inclinical trials, ABT-263, and Gossypol), PARP inhibitors (e.g. Iniparib,Olaparib in clinical trials), PI3K inhibitors (eg. perifosine in a phaseIII trial), VEGF Receptor 2 inhibitors (e.g. Apatinib), AN-152,(AEZS-108), Braf inhibitors (e.g. vemurafenib, dabrafenib and LGX818),MEK inhibitors (e.g. trametinib and MEK162), CDK inhibitors, (e.g.PD-0332991), salinomycin and Sorafenib; (j) Chemotherapy usingmonoclonal antibodies such as Rituximab (marketed as MABTHERA® orRITUXAN®), Trastuzumab (Herceptin also known as ErbB2), Cetuximab(marketed as ERBITUX®), and Bevacizumab (marketed as AVASTIN®); and (k)radiation therapy.

In some embodiments, diabetic retinopathy can be treated with acombination of a compound of Formula (I) and one or more of thefollowing natural supplements: Bilberry, Butcher's broom, Ginkgo, Grapeseed extract, and Pycnogenol (Pine bark).

In some embodiments, idiopathic pulmonary fibrosis/pulmonary fibrosiscan be treated with a combination of a compound of Formula (I) and oneor more of the following drugs: pirfenidone (pirfenidone was approvedfor use in 2011in Europe under the brand name Esbriet®), prednisone,azathioprine, N-acetylcysteine, interferon-γ 1b, bosentan (bosentan iscurrently being studied in patients with IPF, [The American Journal ofRespiratory and Critical Care Medicine (2011), 184(1), 92-9]),Nintedanib (BIBF 1120 and Vargatef), QAX576 [British Journal ofPharmacology (2011), 163(1), 141-172], and anti-inflammatory agents suchas corticosteroids.

In some embodiments, a compound of Formula (I) can be used to treatidiopathic pulmonary fibrosis/pulmonary fibrosis in combination with anyof the following methods: oxygen therapy, pulmonary rehabilitation andsurgery.

In some embodiments, a compound of Formula (I) can be used to treatosteoarthritis in combination with any of the following methods: (a)Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen,naproxen, aspirin and acetaminophen; (b) physical therapy; (c)injections of corticosteroid medications; (d) injections of hyaluronicacid derivatives (e.g. Hyalgan, Synvisc); (e) narcotics, like codeine;(f) in combination with braces and/or shoe inserts or any device thatcan immobilize or support your joint to help you keep pressure off it(e.g., splints, braces, shoe inserts or other medical devices); (g)realigning bones (osteotomy); (h) joint replacement (arthroplasty); and(i) in combination with a chronic pain class.

In some embodiments, macular degeneration can be treated with acombination of a compound of Formula (I) and one or more of thefollowing drugs: Bevacizumab (Avastin®), Ranibizumab (Lucentis®),Pegaptanib (Macugen), Aflibercept (Eylea®), verteporfin) (Visudyne®) incombination with photodynamic therapy (PDT) or with any of the followingmethods: (a) in combination with laser to destroy abnormal blood vessels(photocoagulation); and (b) in combination with increased vitamin intakeof antioxidant vitamins and zinc.

In some embodiments, retinitis pigmentosa can be treated with acombination of a compound of Formula (I) and one or more of thefollowing drugs: UF-021(Ocuseva™) vitamin A palmitate and pikachurin orwith any of the following methods: (a) with the Argus® II retinalimplant; and (b) with stem cell and/or gene therapy.

Administration of the compounds disclosed herein or the pharmaceuticallyacceptable salts thereof can be via any of the accepted modes ofadministration, including, but not limited to, orally, subcutaneously,intravenously, intranasally, topically, transdermally,intraperitoneally, intramuscularly, intrapulmonarilly, vaginally,rectally, ontologically, neuro-otologically, intraocularly,subconjuctivally, via anterior eye chamber injection, intravitreally,intraperitoneally, intrathecally, intracystically, intrapleurally, viawound irrigation, intrabuccally, intra-abdominally, intra-articularly,intra-aurally, intrabronchially, intracapsularly, intrameningeally, viainhalation, via endotracheal or endobronchial instillation, via directinstillation into pulmonary cavities, intraspinally, intrasynovially,intrathoracically, via thoracostomy irrigation, epidurally,intratympanically, intracisternally, intravascularly,intraventricularly, intraosseously, via irrigation of infected bone, orvia application as part of any admixture with a prosthetic devices. Insome embodiments, the administration method includes oral or parenteraladministration.

Compounds provided herein intended for pharmaceutical use may beadministered as crystalline or amorphous products. Pharmaceuticallyacceptable compositions may include solid, semi-solid, liquid,solutions, colloidal, liposomes, emulsions, suspensions, complexes,coacervates and aerosols. Dosage forms, such as, e.g., tablets,capsules, powders, liquids, suspensions, suppositories, aerosols,implants, controlled release or the like. They may be obtained, forexample, as solid plugs, powders, or films by methods such asprecipitation, crystallization, milling, grinding, supercritical fluidprocessing, coacervation, complex coacervation, encapsulation,emulsification, complexation, freeze drying, spray drying, orevaporative drying. Microwave or radio frequency drying may be used forthis purpose. The compounds can also be administered in sustained orcontrolled release dosage forms, including depot injections, osmoticpumps, pills (tablets and or capsules), transdermal (includingelectrotransport) patches, implants and the like, for prolonged and/ortimed, pulsed administration at a predetermined rate.

The compounds can be administered either alone or in combination with aconventional pharmaceutical carrier, excipient or the like.Pharmaceutically acceptable excipients include, but are not limited to,ion exchangers, alumina, aluminum stearate, lecithin, self-emulsifyingdrug delivery systems (SEDDS) such as d-a-tocopherol polyethylene glycol1000 succinate, surfactants used in pharmaceutical dosage forms such asTweens, poloxamers or other similar polymeric delivery matrices, serumproteins, such as human serum albumin, buffer substances such asphosphates, tris, glycine, sorbic acid, potassium sorbate, partialglyceride mixtures of saturated vegetable fatty acids, water, salts orelectrolytes, such as protamine sulfate, disodium hydrogen phosphate,potassium hydrogen phosphate, sodium-chloride, zinc salts, colloidalsilica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-basedsubstances, polyethylene glycol, sodium carboxymethyl cellulose,polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, andwool fat. Cyclodextrins such as α-, β, and γ-cyclodextrin, or chemicallymodified derivatives such as hydroxyalkylcyclodextrins, including 2- and3-hydroxypropyl-β-cyclodextrins, or other solubilized derivatives canalso be used to enhance delivery of compounds described herein. Dosageforms or compositions containing a compound as described herein in therange of 0.005% to 100% with the balance made up from non-toxic carriermay be prepared. The contemplated compositions may contain 0.001%-100%of a compound provided herein, in one embodiment 0.1-95%, in anotherembodiment 75-85%, in a further embodiment 20-80%. Actual methods ofpreparing such dosage forms are known, or will be apparent, to thoseskilled in this art; for example, see Remington: The Science andPractice of Pharmacy, 22^(nd) Edition (Pharmaceutical Press, London, UK.2012).

In one embodiment, the compositions will take the form of a unit dosageform such as a pill or tablet and thus the composition may contain,along with a compound provided herein, a diluent such as lactose,sucrose, dicalcium phosphate, or the like; a lubricant such as magnesiumstearate or the like; and a binder such as starch, gum acacia,polyvinylpyrrolidine, gelatin, cellulose, cellulose derivatives or thelike. In another solid dosage form, a powder, marume, solution orsuspension (e.g., in propylene carbonate, vegetable oils, PEG's,poloxamer 124 or triglycerides) is encapsulated in a capsule (gelatin orcellulose base capsule). Unit dosage forms in which one or morecompounds provided herein or additional active agents are physicallyseparated are also contemplated; e.g., capsules with granules (ortablets in a capsule) of each drug; two-layer tablets; two-compartmentgel caps, etc. Enteric coated or delayed release oral dosage forms arealso contemplated.

Liquid pharmaceutically administrable compositions can, for example, beprepared by dissolving, dispersing, etc. a compound provided herein andoptional pharmaceutical adjuvants in a carrier (e.g., water, saline,aqueous dextrose, glycerol, glycols, ethanol or the like) to form asolution, colloid, liposome, emulsion, complexes, coacervate orsuspension. If desired, the pharmaceutical composition can also containminor amounts of nontoxic auxiliary substances such as wetting agents,emulsifying agents, co-solvents, solubilizing agents, pH bufferingagents and the like (e.g., sodium acetate, sodium citrate, cyclodextrinderivatives, sorbitan monolaurate, triethanolamine acetate,triethanolamine oleate, and the like).

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.25 mg/Kg to about 50 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.25 mg/Kg to about 20 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.50 mg/Kg to about 19 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 0.75 mg/Kg to about 18 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.0 mg/Kg to about 17 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.25 mg/Kg to about 16 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.50 mg/Kg to about 15 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 1.75 mg/Kg to about 14 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 2.0 mg/Kg to about 13 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 3.0 mg/Kg to about 12 mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 4.0 mg/Kg to about 11mg/Kg in humans.

In some embodiments, the unit dosage of compounds of Formula (I) isabout 5.0 mg/Kg to about 10 mg/Kg in humans.

In some embodiments, the compositions are provided in unit dosage formssuitable for single administration.

In some embodiments, the compositions are provided in unit dosage formssuitable for twice a day administration.

In some embodiments, the compositions are provided in unit dosage formssuitable for three times a day administration.

Injectables can be prepared in conventional forms, either as liquidsolutions, colloid, liposomes, complexes, coacervate or suspensions, asemulsions, or in solid forms suitable for reconstitution in liquid priorto injection. The percentage of a compound provided herein contained insuch parenteral compositions is highly dependent on the specific naturethereof, as well as the activity of the compound and the needs of thepatient. However, percentages of active ingredient of 0.01% to 10% insolution are employable, and could be higher if the composition is asolid or suspension, which could be subsequently diluted to the abovepercentages.

In some embodiments, the composition will comprise about 0.1-10% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.1-5% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.1-4% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.15-3% of theactive agent in solution.

In some embodiments, the composition will comprise about 0.2-2% of theactive agent in solution.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-96 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-72 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-48 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-24 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-12 hours.

In some embodiments, the compositions are provided in dosage formssuitable for continuous dosage by intravenous infusion over a period ofabout 1-6 hours.

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 5 mg/m² to about 300mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 5 mg/m² to about 200mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 5 mg/m² to about 100mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 10 mg/m² to about 50mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 50 mg/m² to about 200mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 75 mg/m² to about 175mg/m².

In some embodiments, these compositions can be administered byintravenous infusion to humans at doses of about 100 mg/m² to about 150mg/m².

It is to be noted that concentrations and dosage values may also varydepending on the specific compound and the severity of the condition tobe alleviated. It is to be further understood that for any particularpatient, specific dosage regimens should be adjusted over time accordingto the individual need and the professional judgment of the personadministering or supervising the administration of the compositions, andthat the concentration ranges set forth herein are exemplary only andare not intended to limit the scope or practice of the claimedcompositions.

In one embodiment, the compositions can be administered to therespiratory tract (including nasal and pulmonary) e.g., through anebulizer, metered-dose inhalers, atomizer, mister, aerosol, dry powderinhaler, insufflator, liquid instillation or other suitable device ortechnique.

In some embodiments, aerosols intended for delivery to the nasal mucosaare provided for inhalation through the nose. For optimal delivery tothe nasal cavities, inhaled particle sizes of about 5 to about 100microns are useful, with particle sizes of about 10 to about 60 micronsbeing preferred. For nasal delivery, a larger inhaled particle size maybe desired to maximize impaction on the nasal mucosa and to minimize orprevent pulmonary deposition of the administered formulation. In someembodiments, aerosols intended for delivery to the lung are provided forinhalation through the nose or the mouth. For delivery to the lung,inhaled aerodynamic particle sizes of about less than 10 μm are useful(e.g., about 1to about 10 microns). Inhaled particles may be defined asliquid droplets containing dissolved drug, liquid droplets containingsuspended drug particles (in cases where the drug is insoluble in thesuspending medium), dry particles of pure drug substance, drug substanceincorporated with excipients, liposomes, emulsions, colloidal systems,coacervates, aggregates of drug nanoparticles, or dry particles of adiluent which contain embedded drug nanoparticles.

In some embodiments, compounds of Formula (I) disclosed herein intendedfor respiratory delivery (either systemic or local) can be administeredas aqueous formulations, as non-aqueous solutions or suspensions, assuspensions or solutions in halogenated hydrocarbon propellants with orwithout alcohol, as a colloidal system, as emulsions, coacervates, or asdry powders. Aqueous formulations may be aerosolized by liquidnebulizers employing either hydraulic or ultrasonic atomization or bymodified micropump systems (like the soft mist inhalers, the Aerodose®or the AERx® systems). Propellant-based systems may use suitablepressurized metered-dose inhalers (pMDIs). Dry powders may use drypowder inhaler devices (DPIs), which are capable of dispersing the drugsubstance effectively. A desired particle size and distribution may beobtained by choosing an appropriate device.

In some embodiments, the compositions of Formula (I) disclosed hereincan be administered to the ear by various methods. For example, a roundwindow catheter (e.g., U.S. Pat. Nos. 6,440,102 and 6,648,873) can beused.

Alternatively, formulations can be incorporated into a wick for usebetween the outer and middle ear (e.g., U.S. Pat. No. 6,120,484) orabsorbed to collagen sponge or other solid support (e.g., U.S. Pat. No.4,164,559).

If desired, formulations of the invention can be incorporated into a gelformulation (e.g., U.S. Pat. Nos. 4,474,752 and 6,911,211).

In some embodiments, compounds of Formula (I) disclosed herein intendedfor delivery to the ear can be administered via an implanted pump anddelivery system through a needle directly into the middle or inner ear(cochlea) or through a cochlear implant stylet electrode channel oralternative prepared drug delivery channel such as but not limited to aneedle through temporal bone into the cochlea.

Other options include delivery via a pump through a thin film coatedonto a multichannel electrode or electrode with a specially imbeddeddrug delivery channel (pathways) carved into the thin film for thispurpose. In other embodiments the acidic or basic solid compound ofFormula (I) can be delivered from the reservoir of an external orinternal implanted pumping system.

Formulations of the invention also can be administered to the ear byintratympanic injection into the middle ear, inner ear, or cochlea(e.g., U.S. Pat. No. 6,377,849 and Ser. No. 11/337,815).

Intratympanic injection of therapeutic agents is the technique ofinjecting a therapeutic agent behind the tympanic membrane into themiddle and/or inner ear. In one embodiment, the formulations describedherein are administered directly onto the round window membrane viatranstympanic injection. In another embodiment, the ion channelmodulating agent auris-acceptable formulations described herein areadministered onto the round window membrane via a non-transtympanicapproach to the inner ear. In additional embodiments, the formulationdescribed herein is administered onto the round window membrane via asurgical approach to the round window membrane comprising modificationof the crista fenestrae cochleae.

In some embodiments, the compounds of Formula (I) are formulated inrectal compositions such as enemas, rectal gels, rectal foams, rectalaerosols, suppositories, jelly suppositories, or retention enemas,containing conventional suppository bases such as cocoa butter or otherglycerides, as well as synthetic polymers such as polyvinylpyrrolidone,PEG (like PEG ointments), and the like.

Suppositories for rectal administration of the drug (either as asolution, colloid, suspension or a complex) can be prepared by mixing acompound provided herein with a suitable non-irritating excipient thatis solid at ordinary temperatures but liquid at the rectal temperatureand will therefore melt or erode/dissolve in the rectum and release thecompound. Such materials include cocoa butter, glycerinated gelatin,hydrogenated vegetable oils, poloxamers, mixtures of polyethyleneglycols of various molecular weights and fatty acid esters ofpolyethylene glycol. In suppository forms of the compositions, alow-melting wax such as, but not limited to, a mixture of fatty acidglycerides, optionally in combination with cocoa butter, is firstmelted.

Solid compositions can be provided in various different types of dosageforms, depending on the physicochemical properties of the compoundprovided herein, the desired dissolution rate, cost considerations, andother criteria. In one of the embodiments, the solid composition is asingle unit. This implies that one unit dose of the compound iscomprised in a single, physically shaped solid form or article. In otherwords, the solid composition is coherent, which is in contrast to amultiple unit dosage form, in which the units are incoherent.

Examples of single units which may be used as dosage forms for the solidcomposition include tablets, such as compressed tablets, film-likeunits, foil-like units, wafers, lyophilized matrix units, and the like.In one embodiment, the solid composition is a highly porous lyophilizedform. Such lyophilizates, sometimes also called wafers or lyophilizedtablets, are particularly useful for their rapid disintegration, whichalso enables the rapid dissolution of the compound.

On the other hand, for some applications the solid composition may alsobe formed as a multiple unit dosage form as defined above. Examples ofmultiple units are powders, granules, microparticles, pellets,mini-tablets, beads, lyophilized powders, and the like. In oneembodiment, the solid composition is a lyophilized powder. Such adispersed lyophilized system comprises a multitude of powder particles,and due to the lyophilization process used in the formation of thepowder, each particle has an irregular, porous microstructure throughwhich the powder is capable of absorbing water very rapidly, resultingin quick dissolution. Effervescent compositions are also contemplated toaid the quick dispersion and absorption of the compound.

Another type of multiparticulate system which is also capable ofachieving rapid drug dissolution is that of powders, granules, orpellets from water-soluble excipients which are coated with a compoundprovided herein so that the compound is located at the outer surface ofthe individual particles. In this type of system, the water-soluble lowmolecular weight excipient may be useful for preparing the cores of suchcoated particles, which can be subsequently coated with a coatingcomposition comprising the compound and, for example, one or moreadditional excipients, such as a binder, a pore former, a saccharide, asugar alcohol, a film-forming polymer, a plasticizer, or otherexcipients used in pharmaceutical coating compositions.

Also provided herein are kits. Typically, a kit includes one or morecompounds or compositions as described herein. In certain embodiments, akit can include one or more delivery systems, e.g., for delivering oradministering a compound as provided herein, and directions for use ofthe kit (e.g., instructions for treating a patient). In anotherembodiment, the kit can include a compound or composition as describedherein and a label that indicates that the contents are to beadministered to a patient with cancer. In another embodiment, the kitcan include a compound or composition as described herein and a labelthat indicates that the contents are to be administered to a patientwith one or more of hepatocellular carcinoma, colon cancer, leukemia,lymphoma, sarcoma, ovarian cancer, diabetic retinopathy, pulmonaryfibrosis, rheumatoid arthritis, sepsis, ankylosing spondylitis,psoriasis, scleroderma, mycotic and viral infections, bone and cartilagediseases, Alzheimer's disease, lung disease, bone/osteoporotic (wrist,spine, shoulder and hip) fractures, articular cartilage (chondral)defects, degenerative disc disease (or intervertebral discdegeneration), polyposis coli, bone density and vascular defects in theeye (Osteoporosis-pseudoglioma Syndrome, OPPG) and other eye diseases orsyndromes associated with defects and/or damaged photoreceptors,familial exudative vitreoretinopathy, retinal angiogenesis, earlycoronary disease, tetra-amelia, Müllerian-duct regression andvirilization, SERKAL syndrome, type II diabetes, Fuhrmann syndrome,Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication, tooth agenesis, Wilms tumor, skeletal dysplasia,focal dermal hypoplasia, autosomal recessive anonychia, neural tubedefects, alpha-thalassemia (ATRX) syndrome, fragile X syndrome, ICFsyndrome, Angelman's syndrome, Prader-Willi syndrome, Beckwith-WiedemannSyndrome, Norrie disease, and Rett syndrome.

Methods of Treatment

The compounds and compositions provided herein can be used as inhibitorsand/or modulators of one or more components of the Wnt pathway, whichmay include one or more Wnt proteins, and thus can be used to treat avariety of disorders and diseases in which aberrant Wnt signaling isimplicated, such as cancer and other diseases associated with abnormalangiogenesis, cellular proliferation, and cell cycling. Accordingly, thecompounds and compositions provided herein can be used to treat cancer,to reduce or inhibit angiogenesis, to reduce or inhibit cellularproliferation, to correct a genetic disorder, and/or to treat aneurological condition/disorder/disease due to mutations ordysregulation of the Wnt pathway and/or of one or more of Wnt signalingcomponents. Non-limiting examples of diseases which can be treated withthe compounds and compositions provided herein include a variety ofcancers, diabetic retinopathy, pulmonary fibrosis, rheumatoid arthritis,scleroderma, mycotic and viral infections, bone and cartilage diseases,neurological conditions/diseases such as Alzheimer's disease,amyotrophic lateral sclerosis (ALS), motor neuron disease, multiplesclerosis or autism, lung disease, bone/osteoporotic (wrist, spine,shoulder and hip) fractures, polyposis coli, bone density and vasculardefects in the eye (Osteoporosis-pseudoglioma Syndrome, OPPG) and othereye diseases or syndromes associated with defects and/or damagedphotoreceptors, familial exudative vitreoretinopathy, retinalangiogenesis, early coronary disease, tetra-amelia, Müllerian-ductregression and virilization, SERKAL syndrome, type II diabetes, Fuhrmannsyndrome, Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication, tooth agenesis, Wilms tumor, skeletal dysplasia,focal dermal hypoplasia, autosomal recessive anonychia, neural tubedefects, alpha-thalassemia (ATRX) syndrome, fragile X syndrome, ICFsyndrome, Angelman's syndrome, Prader-Willi syndrome, Beckwith-WiedemannSyndrome, Norrie disease and Rett syndrome.

In some embodiments, non-limiting examples of eye diseases which can betreated with the compounds and compositions provided herein includeage-related macular degeneration (AMD or ARMD), rod cone dystrophy,retinitis pigmentosa (RP), acute idiopathic blind spot enlargement(AIBSE), acute zonal occult outer retinopathy (AZOOR), acute macularneuroretinopathy (AMN), multiple evanescent white dot syndrome (MEWDS),multifocal choroiditis, opticneuropathy. Further causes of photoreceptordamage that can be treated with the compounds and compositions providedherein include retinal detachment, vascular disturbance, eye tumors orextreme light damage.

With respect to cancer, the Wnt pathway is known to be constitutivelyactivated in a variety of cancers including, for example, colon cancer,hepatocellular carcinoma, lung cancer, ovarian cancer, prostate cancer ,pancreatic cancer and leukemias such as CML, CLL and T-ALL. Accordingly,the compounds and compositions described herein may be used to treatthese cancers in which the Wnt pathway is constitutively activated. Incertain embodiments, the cancer is chosen from hepatocellular carcinoma,colon cancer, leukemia, lymphoma, sarcoma and ovarian cancer.

Other cancers can also be treated with the compounds and compositionsdescribed herein.

More particularly, cancers that may be treated by the compounds,compositions and methods described herein include, but are not limitedto, the following:

1) Breast cancers, including, for example ER⁺ breast cancer, ER⁻ breastcancer, her2⁻ breast cancer, her2⁺ breast cancer, stromal tumors such asfibroadenomas, phyllodes tumors, and sarcomas, and epithelial tumorssuch as large duct papillomas; carcinomas of the breast including insitu (noninvasive) carcinoma that includes ductal carcinoma in situ(including Paget's disease) and lobular carcinoma in situ, and invasive(infiltrating) carcinoma including, but not limited to, invasive ductalcarcinoma, invasive lobular carcinoma, medullary carcinoma, colloid(mucinous) carcinoma, tubular carcinoma, and invasive papillarycarcinoma; and miscellaneous malignant neoplasms. Further examples ofbreast cancers can include luminal A, luminal B, basal A, basal B, andtriple negative breast cancer, which is estrogen receptor negative(ER⁻), progesterone receptor negative, and her2 negative (her2⁻). Insome embodiments, the breast cancer may have a high risk Oncotype score.

2) Cardiac cancers, including, for example sarcoma, e.g., angiosarcoma,fibrosarcoma, rhabdomyosarcoma, and liposarcoma; myxoma; rhabdomyoma;fibroma; lipoma and teratoma.

3) Lung cancers, including, for example, bronchogenic carcinoma, e.g.,squamous cell, undifferentiated small cell, undifferentiated large cell,and adenocarcinoma; alveolar and bronchiolar carcinoma; bronchialadenoma; sarcoma; lymphoma; chondromatous hamartoma; and mesothelioma.

4) Gastrointestinal cancer, including, for example, cancers of theesophagus, e.g., squamous cell carcinoma, adenocarcinoma,leiomyosarcoma, and lymphoma; cancers of the stomach, e.g., carcinoma,lymphoma, and leiomyosarcoma; cancers of the pancreas, e.g., ductaladenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors,and vipoma; cancers of the small bowel, e.g., adenocarcinoma, lymphoma,carcinoid tumors, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma,neurofibroma, and fibroma; cancers of the large bowel, e.g.,adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, andleiomyoma.

5) Genitourinary tract cancers, including, for example, cancers of thekidney, e.g., adenocarcinoma, Wilm's tumor (nephroblastoma), lymphoma,and leukemia; cancers of the bladder and urethra, e.g., squamous cellcarcinoma, transitional cell carcinoma, and adenocarcinoma; cancers ofthe prostate, e.g., adenocarcinoma, and sarcoma; cancer of the testis,e.g., seminoma, teratoma, embryonal carcinoma, teratocarcinoma,choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma,fibroadenoma, adenomatoid tumors, and lipoma.

6) Liver cancers, including, for example, hepatoma, e.g., hepatocellularcarcinoma; cholangiocarcinoma; hepatoblastoma; angiosarcoma;hepatocellular adenoma; and hemangioma.

7) Bone cancers, including, for example, osteogenic sarcoma(osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma,chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cellsarcoma), multiple myeloma, malignant giant cell tumor chordoma,osteochrondroma (osteocartilaginous exostoses), benign chondroma,chondroblastoma, chondromyxofibroma, osteoid osteoma and giant celltumors.

8) Nervous system cancers, including, for example, cancers of the skull,e.g., osteoma, hemangioma, granuloma, xanthoma, and osteitis deformans;cancers of the meninges, e.g., meningioma, meningiosarcoma, andgliomatosis; cancers of the brain, e.g., astrocytoma, medulloblastoma,glioma, ependymoma, germinoma (pinealoma), glioblastoma multiform,oligodendroglioma, schwannoma, retinoblastoma, and congenital tumors;and cancers of the spinal cord, e.g., neurofibroma, meningioma, glioma,and sarcoma.

9) Gynecological cancers, including, for example, cancers of the uterus,e.g., endometrial carcinoma; cancers of the cervix, e.g., cervicalcarcinoma, and pre tumor cervical dysplasia; cancers of the ovaries,e.g., ovarian carcinoma, including serous cystadenocarcinoma, mucinouscystadenocarcinoma, unclassified carcinoma, granulosa theca cell tumors,Sertoli Leydig cell tumors, dysgerminoma, and malignant teratoma;cancers of the vulva, e.g., squamous cell carcinoma, intraepithelialcarcinoma, adenocarcinoma, fibrosarcoma, and melanoma; cancers of thevagina, e.g., clear cell carcinoma, squamous cell carcinoma, botryoidsarcoma, and embryonal rhabdomyosarcoma; and cancers of the fallopiantubes, e.g., carcinoma.

10) Hematologic cancers, including, for example, cancers of the blood,e.g., acute myeloid leukemia, chronic myeloid leukemia, acutelymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferativediseases, multiple myeloma, and myelodysplastic syndrome, Hodgkin'slymphoma, non-Hodgkin's lymphoma (malignant lymphoma) and Waldenstrom'smacroglobulinemia.

11) Skin cancers and skin disorders, including, for example, malignantmelanoma and metastatic melanoma, basal cell carcinoma, squamous cellcarcinoma, Kaposi's sarcoma, moles dysplastic nevi, lipoma, angioma,dermatofibroma, keloids, and scleroderma.

12) Adrenal gland cancers, including, for example, neuroblastoma.

Cancers may be solid tumors that may or may not be metastatic. Cancersmay also occur, as in leukemia, as a diffuse tissue. Thus, the term“tumor cell,” as provided herein, includes a cell afflicted by any oneof the above identified disorders.

A method of treating cancer using a compound or composition as describedherein may be combined with existing methods of treating cancers, forexample by chemotherapy, irradiation, or surgery (e.g., oophorectomy).In some embodiments, a compound or composition can be administeredbefore, during, or after another anticancer agent or treatment.

The compounds and compositions described herein can be used asanti-angiogenesis agents and as agents for modulating and/or inhibitingthe activity of protein kinases, thus providing treatments for cancerand other diseases associated with cellular proliferation mediated byprotein kinases. For example, the compounds described herein can inhibitthe activity of one or more kinases. Accordingly, provided herein is amethod of treating cancer or preventing or reducing angiogenesis throughkinase inhibition.

In addition, and including treatment of cancer, the compounds andcompositions described herein can function as cell-cycle control agentsfor treating proliferative disorders in a patient. Disorders associatedwith excessive proliferation include, for example, cancers, scleroderma,immunological disorders involving undesired proliferation of leukocytes,and restenosis and other smooth muscle disorders. Furthermore, suchcompounds may be used to prevent de-differentiation of post-mitotictissue and/or cells.

Diseases or disorders associated with uncontrolled or abnormal cellularproliferation include, but are not limited to, the following:

-   -   a variety of cancers, including, but not limited to, carcinoma,        hematopoietic tumors of lymphoid lineage, hematopoietic tumors        of myeloid lineage, tumors of mesenchymal origin, tumors of the        central and peripheral nervous system and other tumors including        melanoma, seminoma and Kaposi's sarcoma.    -   a disease process which features abnormal cellular        proliferation, e.g., benign prostatic hyperplasia, familial        adenomatosis polyposis, neurofibromatosis, atherosclerosis,        arthritis, glomerulonephritis, restenosis following angioplasty        or vascular surgery, inflammatory bowel disease, transplantation        rejection, endotoxic shock, and fungal infections. Fibrotic        disorders such as skin fibrosis; scleroderma; progressive        systemic fibrosis; lung fibrosis; muscle fibrosis; kidney        fibrosis; glomerulosclerosis; glomerulonephritis; hypertrophic        scar formation; uterine fibrosis; renal fibrosis; cirrhosis of        the liver, liver fibrosis; fatty liver disease (FLD); adhesions,        such as those occurring in the abdomen, pelvis, spine or        tendons; chronic obstructive pulmonary disease; fibrosis        following myocardial infarction; pulmonary fibrosis; fibrosis        and scarring associated with diffuse/interstitial lung disease;        central nervous system fibrosis, such as fibrosis following        stroke; fibrosis associated with neuro-degenerative disorders        such as Alzheimer's Disease or multiple sclerosis; fibrosis        associated with proliferative vitreoretinopathy (PVR);        restenosis; endometriosis; ischemic disease and radiation        fibrosis.    -   defective apoptosis-associated conditions, such as cancers        (including but not limited to those types mentioned herein),        viral infections (including but not limited to herpesvirus,        poxvirus, Epstein-Barr virus, Sindbis virus and adenovirus),        prevention of AIDS development in HIV-infected individuals,        autoimmune diseases (including but not limited to systemic lupus        erythematosus, rheumatoid arthritis, sepsis, ankylosing        spondylitis, psoriasis, scleroderma, autoimmune mediated        glomerulonephritis, inflammatory bowel disease and autoimmune        diabetes mellitus), neuro-degenerative disorders (including but        not limited to Alzheimer's disease, lung disease, amyotrophic        lateral sclerosis, retinitis pigmentosa, Parkinson's disease,        AIDS-related dementia, spinal muscular atrophy and cerebellar        degeneration), myelodysplastic syndromes, aplastic anemia,        ischemic injury associated with myocardial infarctions, stroke        and reperfusion injury, arrhythmia, atherosclerosis,        toxin-induced or alcohol related liver diseases, hematological        diseases (including but not limited to chronic anemia and        aplastic anemia), degenerative diseases of the musculoskeletal        system (including but not limited to osteoporosis and        arthritis), tendinopathies such as tendinitis and tendinosis,        aspirin-sensitive rhinosinusitis, cystic fibrosis, multiple        sclerosis, kidney diseases and cancer pain.    -   genetic diseases due to mutations in Wnt signaling components,        such as polyposis coli, bone density and vascular defects in the        eye (Osteoporosis-pseudoglioma Syndrome, OPPG) and other eye        diseases or syndromes associated with defects and/or damaged        photoreceptors, familial exudative vitreoretinopathy, retinal        angiogenesis, early coronary disease, tetra-amelia,        Mullerian-duct regression and virilization, SERKAL syndrome,        type II diabetes, Fuhrmann syndrome,        Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,        odonto-onycho-dermal dysplasia, obesity, split-hand/foot        malformation, caudal duplication, tooth agenesis, Wilms tumor,        skeletal dysplasia, focal dermal hypoplasia, autosomal recessive        anonychia, neural tube defects, alpha-thalassemia (ATRX)        syndrome, fragile X syndrome, ICF syndrome, Angelman's syndrome,        Prader-Willi syndrome, Beckwith-Wiedemann Syndrome, Norrie        disease and Rett syndrome.

The compounds and compositions described herein can be used to treatneurological conditions, disorders and/or diseases caused by dysfunctionin the Wnt signaling pathway. Non-limiting examples of neurologicalconditions/disorders/diseases which can be treated with the compoundsand compositions provided herein include Alzheimer's disease, aphasia,apraxia, arachnoiditis, ataxia telangiectasia, attention deficithyperactivity disorder, auditory processing disorder, autism,alcoholism, Bell's palsy, bipolar disorder, brachial plexus injury,Canavan disease, carpal tunnel syndrome, causalgia, central painsyndrome, central pontine myelinolysis, centronuclear myopathy, cephalicdisorder, cerebral aneurysm, cerebral arteriosclerosis, cerebralatrophy, cerebral gigantism, cerebral palsy, cerebral vasculitis,cervical spinal stenosis, Charcot-Marie-Tooth disease, Chiarimalformation, chronic fatigue syndrome, chronic inflammatorydemyelinating polyneuropathy (CIDP), chronic pain, Coffin—Lowrysyndrome, complex regional pain syndrome, compression neuropathy,congenital facial diplegia, corticobasal degeneration, cranialarteritis, craniosynostosis, Creutzfeldt-Jakob disease, cumulativetrauma disorder, Cushing's syndrome, cytomegalic inclusion body disease(CIBD), Dandy-Walker syndrome, Dawson disease, de Morsier's syndrome,Dejerine-Klumpke palsy, Dejerine-Sottas disease, delayed sleep phasesyndrome, dementia, dermatomyositis, developmental dyspraxia, diabeticneuropathy, diffuse sclerosis, Dravet syndrome, dysautonomia,dyscalculia, dysgraphia, dyslexia, dystonia, empty sella syndrome,encephalitis, encephalocele, encephalotrigeminal angiomatosis,encopresis, epilepsy, Erb's palsy, erythromelalgia, essential tremor,Fabry's disease, Fahr's syndrome, familial spastic paralysis, febrileseizure, Fisher syndrome, Friedreich's ataxia, fibromyalgia, Foville'ssyndrome, Gaucher's disease, Gerstmann's syndrome, giant cell arteritis,giant cell inclusion disease, globoid cell leukodystrophy, gray matterheterotopia, Guillain-Barré syndrome, HTLV-1associated myelopathy,Hallervorden-Spatz disease, hemifacial spasm, hereditary spasticparaplegia, heredopathia atactica polyneuritiformis, herpes zosteroticus, herpes zoster, Hirayama syndrome, holoprosencephaly,Huntington's disease, hydranencephaly, hydrocephalus, hypercortisolism,hypoxia, immune-mediated encephalomyelitis, inclusion body myositis,incontinentia pigmenti, infantile phytanic acid storage disease,infantile Refsum disease, infantile spasms, inflammatory myopathy,intracranial cyst, intracranial hypertension, Joubert syndrome, Karaksyndrome, Kearns-Sayre syndrome, Kennedy disease, Kinsbourne syndrome,Klippel Feil syndrome, Krabbe disease, Kugelberg-Welander disease, kuru,Lafora disease, Lambert-Eaton myasthenic syndrome, Landau-Kleffnersyndrome, lateral medullary (Wallenberg) syndrome, Leigh's disease,Lennox-Gastaut syndrome, Lesch-Nyhan syndrome, leukodystrophy, Lewy bodydementia, lissencephaly, locked-in syndrome, Lou Gehrig's disease,lumbar disc disease, lumbar spinal stenosis, Lyme disease,Machado-Joseph disease (Spinocerebellar ataxia type 3), macrencephaly,macropsia, megalencephaly, Melkersson-Rosenthal syndrome, Meniere'sdisease, meningitis, Menkes disease, metachromatic leukodystrophy,microcephaly, micropsia, Miller Fisher syndrome, misophonia,mitochondrial myopathy, Mobius syndrome, monomelic amyotrophy, motorneuron disease, motor skills disorder, Moyamoya disease,mucopolysaccharidoses, multi-infarct dementia, multifocal motorneuropathy, multiple sclerosis, multiple system atrophy, musculardystrophy, myalgic encephalomyelitis, myasthenia gravis, myelinoclasticdiffuse sclerosis, myoclonic Encephalopathy of infants, myoclonus,myopathy, myotubular myopathy, myotonia congenital, narcolepsy,neurofibromatosis, neuroleptic malignant syndrome, lupus erythematosus,neuromyotonia, neuronal ceroid lipofuscinosis, Niemann-Pick disease,O'Sullivan-McLeod syndrome, occipital Neuralgia, occult SpinalDysraphism Sequence, Ohtahara syndrome, olivopontocerebellar atrophy,opsoclonus myoclonus syndrome, optic neuritis, orthostatic hypotension,palinopsia, paresthesia, Parkinson's disease, paramyotonia Congenita,paraneoplastic diseases, paroxysmal attacks, Parry-Romberg syndrome,Pelizaeus-Merzbacher disease, periodic paralyses, peripheral neuropathy,photic sneeze reflex, phytanic acid storage disease, Pick's disease,polymicrogyria (PMG), polymyositis, porencephaly, post-polio syndrome,postherpetic neuralgia (PHN), postural hypotension, Prader-Willisyndrome, primary lateral sclerosis, prion diseases, progressivehemifacial atrophy, progressive multifocal leukoencephalopathy,progressive supranuclear palsy, pseudotumor cerebri, Ramsay Huntsyndrome type I, Ramsay Hunt syndrome type II, Ramsay Hunt syndrome typeIII, Rasmussen's encephalitis, reflex neurovascular dystrophy, Refsumdisease, restless legs syndrome, retrovirus-associated myelopathy, Rettsyndrome, Reye's syndrome, rhythmic movement disorder, Romberg syndrome,Saint Vitus dance, Sandhoff disease, schizophrenia, Schilder's disease,schizencephaly, sensory integration dysfunction, septo-optic dysplasia,Shy-Drager syndrome, Sjogren's syndrome, snatiation, Sotos syndrome,spasticity, spina bifida, spinal cord tumors, spinal muscular atrophy,spinocerebellar ataxia, Steele-Richardson-Olszewski syndrome,Stiff-person syndrome, stroke, Sturge-Weber syndrome, subacutesclerosing panencephalitis, subcortical arteriosclerotic encephalopathy,superficial siderosis, Sydenham's chorea, syncope, synesthesia,syringomyelia, tarsal tunnel syndrome, tardive dyskinesia, tardivedysphrenia, Tarlov cyst, Tay-Sachs disease, temporal arteritis, tetanus,tethered spinal cord syndrome, Thomsen disease, thoracic outletsyndrome, tic douloureux, Todd's paralysis, Tourette syndrome, toxicencephalopathy, transient ischemic attack, transmissible spongiformencephalopathies, transverse myelitis, tremor, trigeminal neuralgia,tropical spastic paraparesis, trypanosomiasis, tuberous sclerosis,ubisiosis, Von Hippel-Lindau disease (VHL), Viliuisk Encephalomyelitis(VE), Wallenberg's syndrome, Werdnig, Hoffman disease, west syndrome,Williams syndrome, Wilson's disease and Zellweger syndrome.

The compounds and compositions may also be useful in the inhibition ofthe development of invasive cancer, tumor angiogenesis and metastasis.

In some embodiments, the disclosure provides a method for treating adisease or disorder associated with aberrant cellular proliferation byadministering to a patient in need of such treatment an effective amountof one or more of the compounds of Formula (I), in combination(simultaneously or sequentially) with at least one other agent.

In some embodiments, the disclosure provides a method of treating orameliorating in a patient a disorder or disease selected from the groupconsisting of: cancer, pulmonary fibrosis, idiopathic pulmonary fibrosis(IPF), degenerative disc disease, bone/osteoporotic fractures, bone orcartilage disease, and osteoarthritis, the method comprisingadministering to the patient a therapeutically effective amount of acompound according to claim 1, or a pharmaceutically acceptable saltthereof

In some embodiments, the pharmaceutical composition comprises atherapeutically effective amount of a compound of Formula (I), or apharmaceutically acceptable salt thereof, and a pharmaceuticallyacceptable excipient.

In some embodiments, the method of treats a disorder or disease in whichaberrant Wnt signaling is implicated in a patient, the method comprisesadministering to the patient a therapeutically effective amount of acompound of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the disorder or disease is cancer.

In some embodiments, the disorder or disease is systemic inflammation.

In some embodiments, the disorder or disease is metastatic melanoma.

In some embodiments, the disorder or disease is fatty liver disease.

In some embodiments, the disorder or disease is liver fibrosis.

In some embodiments, the disorder or disease is tendonitis.

In some embodiments, the disorder or disease is damage to a tendon whichwould benefit from tendon regeneration.

In some embodiments, the disorder or disease is diabetes.

In some embodiments, the disorder or disease is degenerative discdisease.

In some embodiments, the disorder or disease is osteoarthritis.

In some embodiments, the disorder or disease is diabetic retinopathy.

In some embodiments, the disorder or disease is pulmonary fibrosis.

In some embodiments, the disorder or disease is idiopathic pulmonaryfibrosis (IPF).

In some embodiments, the disorder or disease is degenerative discdisease.

In some embodiments, the disorder or disease is rheumatoid arthritis.

In some embodiments, the disorder or disease is scleroderma.

In some embodiments, the disorder or disease is a mycotic or viralinfection.

In some embodiments, the disorder or disease is a bone or cartilagedisease.

In some embodiments, the disorder or disease is Alzheimer's disease.

In some embodiments, the disorder or disease is osteoarthritis.

In some embodiments, the disorder or disease is lung disease

In some embodiments, the disorder or disease is a genetic disease causedby mutations in Wnt signaling components, wherein the genetic disease isselected from: polyposis coli, osteoporosis-pseudoglioma syndrome,familial exudative vitreoretinopathy, retinal angiogenesis, earlycoronary disease, tetra-amelia syndrome, Müllerian-duct regression andvirilization, SERKAL syndrome, diabetes mellitus type 2, Fuhrmannsyndrome, Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome,odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation,caudal duplication syndrome, tooth agenesis, Wilms tumor, skeletaldysplasia, focal dermal hypoplasia, autosomal recessive anonychia,neural tube defects, alpha-thalassemia (ATRX) syndrome, fragile Xsyndrome, ICF syndrome, Angelman syndrome, Prader-Willi syndrome,Beckwith-Wiedemann Syndrome, Norrie disease and Rett syndrome.

In some embodiments, the patient is a human.

In some embodiments, the cancer is chosen from: hepatocellularcarcinoma, colon cancer, breast cancer, pancreatic cancer, chronicmyeloid leukemia (CML), chronic myelomonocytic leukemia, chroniclymphocytic leukemia (CLL), acute myeloid leukemia, acute lymphocyticleukemia, Hodgkin lymphoma, lymphoma, sarcoma and ovarian cancer.

In some embodiments, the cancer is chosen from: lung cancer—non-smallcell, lung cancer—small cell, multiple myeloma, nasopharyngeal cancer,neuroblastoma, osteosarcoma, penile cancer, pituitary tumors, prostatecancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, skincancer—basal and squamous cell, skin cancer—melanoma, small intestinecancer, stomach (gastric) cancers, testicular cancer, thymus cancer,thyroid cancer, uterine sarcoma, vaginal cancer, vulvar cancer,laryngeal or hypopharyngeal cancer, kidney cancer, Kaposi sarcoma,gestational trophoblastic disease, gastrointestinal stromal tumor,gastrointestinal carcinoid tumor, gallbladder cancer, eye cancer(melanoma and lymphoma), Ewing tumor, esophagus cancer, endometrialcancer, colorectal cancer, cervical cancer, brain or spinal cord tumor,bone metastasis, bone cancer, bladder cancer, bile duct cancer, analcancer and adrenal cortical cancer.

In some embodiments, the cancer is hepatocellular carcinoma.

In some embodiments, the cancer is colon cancer.

In some embodiments, the cancer is colorectal cancer.

In some embodiments, the cancer is breast cancer.

In some embodiments, the cancer is pancreatic cancer.

In some embodiments, the cancer is chronic myeloid leukemia (CML).

In some embodiments, the cancer is chronic myelomonocytic leukemia.

In some embodiments, the cancer is chronic lymphocytic leukemia (CLL).

In some embodiments, the cancer is acute myeloid leukemia.

In some embodiments, the cancer is acute lymphocytic leukemia.

In some embodiments, the cancer is Hodgkin lymphoma.

In some embodiments, the cancer is lymphoma.

In some embodiments, the cancer is sarcoma.

In some embodiments, the cancer is ovarian cancer.

In some embodiments, the cancer is lung cancer—non-small cell.

In some embodiments, the cancer is lung cancer—small cell.

In some embodiments, the cancer is multiple myeloma.

In some embodiments, the cancer is nasopharyngeal cancer.

In some embodiments, the cancer is neuroblastoma.

In some embodiments, the cancer is osteosarcoma.

In some embodiments, the cancer is penile cancer.

In some embodiments, the cancer is pituitary tumors.

In some embodiments, the cancer is prostate cancer.

In some embodiments, the cancer is retinoblastoma.

In some embodiments, the cancer is rhabdomyosarcoma.

In some embodiments, the cancer is salivary gland cancer.

In some embodiments, the cancer is skin cancer—basal and squamous cell.

In some embodiments, the cancer is skin cancer—melanoma.

In some embodiments, the cancer is small intestine cancer.

In some embodiments, the cancer is stomach (gastric) cancers.

In some embodiments, the cancer is testicular cancer.

In some embodiments, the cancer is thymus cancer.

In some embodiments, the cancer is thyroid cancer.

In some embodiments, the cancer is uterine sarcoma.

In some embodiments, the cancer is vaginal cancer.

In some embodiments, the cancer is vulvar cancer.

In some embodiments, the cancer is Wilms tumor.

In some embodiments, the cancer is laryngeal or hypopharyngeal cancer.

In some embodiments, the cancer is kidney cancer.

In some embodiments, the cancer is Kaposi sarcoma.

In some embodiments, the cancer is gestational trophoblastic disease.

In some embodiments, the cancer is gastrointestinal stromal tumor.

In some embodiments, the cancer is gastrointestinal carcinoid tumor.

In some embodiments, the cancer is gallbladder cancer.

In some embodiments, the cancer is eye cancer (melanoma and lymphoma).

In some embodiments, the cancer is Ewing tumor.

In some embodiments, the cancer is esophagus cancer.

In some embodiments, the cancer is endometrial cancer.

In some embodiments, the cancer is colorectal cancer.

In some embodiments, the cancer is cervical cancer.

In some embodiments, the cancer is brain or spinal cord tumor.

In some embodiments, the cancer is bone metastasis.

In some embodiments, the cancer is bone cancer.

In some embodiments, the cancer is bladder cancer.

In some embodiments, the cancer is bile duct cancer.

In some embodiments, the cancer is anal cancer.

In some embodiments, the cancer is adrenal cortical cancer.

In some embodiments, the disorder or disease is a neurologicalcondition, disorder or disease, wherein the neurologicalcondition/disorder/disease is selected from: Alzheimer's disease,frontotemporal dementias, dementia with lewy bodies, prion diseases,Parkinson's disease, Huntington's disease, progressive supranuclearpalsy, corticobasal degeneration, multiple system atrophy, amyotrophiclateral sclerosis (ALS), inclusion body myositis, autism, degenerativemyopathies, diabetic neuropathy, other metabolic neuropathies, endocrineneuropathies, orthostatic hypotension, multiple sclerosis andCharcot-Marie-Tooth disease.

In some embodiments, the compound of Formula (I) inhibits one or moreproteins in the Wnt pathway.

In some embodiments, the compound of Formula (I) inhibits signalinginduced by one or more Wnt proteins.

In some embodiments, the Wnt proteins are chosen from: WNT1, WNT2,WNT2B, WNT3, WNT3A, WNT4. WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A,WNT8B, WNT9A, WNT9B, WNT10A, WNT10B, WNT11, and WNT16.

In some embodiments, the method inhibits one or more proteins in the Wntpathway, the method comprises contacting a cell with an effective amountof a compound of Formula (I).

In some embodiments, the cell is a human cell.

In some embodiments, the human cell is a cancerous cell.

In some embodiments, the cancerous cell is a colon cancer cell.

In some embodiments, the contacting is in vitro.

In some embodiments, the compound of Formula (I) inhibits a kinaseactivity.

In some embodiments, the method treats a disease or disorder mediated bythe Wnt pathway in a patient, the method comprises administering to thepatient a therapeutically effective amount of a compound (or compounds)of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the compound of Formula (I) inhibits one or moreWnt proteins.

In some embodiments, the method treats a disease or disorder mediated bykinase activity in a patient, the method comprises administering to thepatient a therapeutically effective amount of a compound (or compounds)of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the disease or disorder comprises tumor growth,cell proliferation, or angiogenesis.

In some embodiments, the method inhibits the activity of a proteinkinase receptor, the method comprises contacting the receptor with aneffective amount of a compound (or compounds) of Formula (I), or apharmaceutically acceptable salt thereof

In some embodiments, the method treats a disease or disorder associatedwith aberrant cellular proliferation in a patient; the method comprisesadministering to the patient a therapeutically effective amount of acompound (or compounds) of Formula (I), or a pharmaceutically acceptablesalt thereof

In some embodiments, the method prevents or reduces angiogenesis in apatient; the method comprises administering to the patient atherapeutically effective amount of a compound (or compounds) of Formula(I), or a pharmaceutically acceptable salt thereof

In some embodiments, the method prevents or reduces abnormal cellularproliferation in a patient; the method comprises administering to thepatient a therapeutically effective amount of a compound (or compounds)of Formula (I), or a pharmaceutically acceptable salt thereof.

In some embodiments, the method treats a disease or disorder associatedwith aberrant cellular proliferation in a patient, the method comprisesadministering to the patient a pharmaceutical composition comprising oneor more of the compounds of claim 1 in combination with apharmaceutically acceptable carrier and one or more other agents.

Moreover, the compounds and compositions, for example, as inhibitors ofthe cyclin-dependent kinases (CDKs), can modulate the level of cellularRNA and DNA synthesis and therefore are expected to be useful in thetreatment of viral infections such as HIV, human papilloma virus, herpesvirus, Epstein-Barr virus, adenovirus, Sindbis virus, pox virus and thelike.

Compounds and compositions described herein can inhibit the kinaseactivity of, for example, CDK/cyclin complexes, such as those active inthe G₀. or G.₁stage of the cell cycle, e.g., CDK2, CDK4, and/or CDK6complexes.

Evaluation of Biological Activity

The biological activity of the compounds described herein can be testedusing any suitable assay known to those of skill in the art, see, e.g.,WO 2001/053268 and WO 2005/009997. For example, the activity of acompound may be tested using one or more of the test methods outlinedbelow.

In one example, tumor cells may be screened for Wnt independent growth.In such a method, tumor cells of interest are contacted with a compound(i.e. inhibitor) of interest, and the proliferation of the cells, e.g.by uptake of tritiated thymidine, is monitored. In some embodiments,tumor cells may be isolated from a candidate patient who has beenscreened for the presence of a cancer that is associated with a mutationin the Wnt signaling pathway. Candidate cancers include, withoutlimitation, those listed above.

In another example, one may utilize in vitro assays for Wnt biologicalactivity, e.g. stabilization of β-catenin and promoting growth of stemcells. Assays for biological activity of Wnt include stabilization ofβ-catenin, which can be measured, for example, by serial dilutions of acandidate inhibitor composition. An exemplary assay for Wnt biologicalactivity contacts a candidate inhibitor with cells containingconstitutively active Wnt/β-catenin signaling. The cells are culturedfor a period of time sufficient to stabilize β-catenin, usually at leastabout 1hour, and lysed. The cell lysate is resolved by SDS PAGE, thentransferred to nitrocellulose and probed with antibodies specific forβ-catenin.

In a further example, the activity of a candidate compound can bemeasured in a Xenopus secondary axis bioassay (Leyns, L. et al. Cell(1997), 88(6), 747-756).

To further illustrate this invention, the following examples areincluded. The examples should not, of course, be construed asspecifically limiting the invention. Variations of these examples withinthe scope of the claims are within the purview of one skilled in the artand are considered to fall within the scope of the invention asdescribed, and claimed herein. The reader will recognize that theskilled artisan, armed with the present disclosure, and skill in the artis able to prepare and use the invention without exhaustive examples.

EXAMPLES Compound preparation

The starting materials used in preparing the compounds of the inventionare known, made by known methods, or are commercially available. It willbe apparent to the skilled artisan that methods for preparing precursorsand functionality related to the compounds claimed herein are generallydescribed in the literature. The skilled artisan given the literatureand this disclosure is well equipped to prepare any of the compounds.

It is recognized that the skilled artisan in the art of organicchemistry can readily carry out manipulations without further direction,that is, it is well within the scope and practice of the skilled artisanto carry out these manipulations. These include reduction of carbonylcompounds to their corresponding alcohols, oxidations, acylations,aromatic substitutions, both electrophilic and nucleophilic,etherifications, esterification and saponification and the like. Thesemanipulations are discussed in standard texts such as March's AdvancedOrganic Chemistry: Reactions, Mechanisms, and Structure 7^(th) Ed., JohnWiley & Sons (2013), Carey and Sundberg, Advanced Organic Chemistry5^(th) Ed., Springer (2007), Comprehensive Organic Transformations: AGuide to Functional Group Transformations, 2^(nd) Ed., John Wiley & Sons(1999) (incorporated herein by reference in its entirety)and the like.

The skilled artisan will readily appreciate that certain reactions arebest carried out when other functionality is masked or protected in themolecule, thus avoiding any undesirable side reactions and/or increasingthe yield of the reaction. Often the skilled artisan utilizes protectinggroups to accomplish such increased yields or to avoid the undesiredreactions. These reactions are found in the literature and are also wellwithin the scope of the skilled artisan. Examples of many of thesemanipulations can be found for example in T. Greene and P. WutsProtective Groups in Organic Synthesis, 4th Ed., John Wiley & Sons(2007), incorporated herein by reference in its entirety.

Trademarks used herein are examples only and reflect illustrativematerials used at the time of the invention. The skilled artisan willrecognize that variations in lot, manufacturing processes, and the like,are expected. Hence the examples, and the trademarks used in them arenon-limiting, and they are not intended to be limiting, but are merelyan illustration of how a skilled artisan may choose to perform one ormore of the embodiments of the invention.

(¹H) nuclear magnetic resonance spectra (NMR) were measured in theindicated solvents on a Bruker NMR spectrometer (Avance TM DRX300, 300MHz for ¹H or Avance TM DRX500, 500 MHz for ¹H) or Varian NMRspectrometer (Mercury 400BB, 400 MHz for ¹H). Peak positions areexpressed in parts per million (ppm) downfield from tetramethylsilane.The peak multiplicities are denoted as follows, s, singlet; d, doublet;t, triplet; q, quartet; ABq, AB quartet; quin, quintet; sex, sextet;sep, septet; non, nonet; dd, doublet of doublets; ddd, doublet ofdoublets of doublets; d/ABq, doublet of AB quartet; dt, doublet oftriplets; td, triplet of doublets; dq, doublet of quartets; m,multiplet.

The following abbreviations have the indicated meanings:

BH₃—Me₂S=borane dimethyl sulfide complex

(Boc)₂O=di-tert-butyl dicarbonate

brine=saturated aqueous sodium chloride

CDCl₃=deuterated chloroform

CDl₃OD=deuterated methanol

DCAD=di-(4-chlorobenzyl)azodicarboxylate

DCE=dichloroethane

DCM=dichloromethane

DEAD=diethyl azodicarboxylate

DHP=dihydropyran

DMAP=4-dimethylaminopyridine

DMF=N,N-dimethylformamide

DMSO-d₆=deuterated dimethylsulfoxide

ESIMS=electron spray mass spectrometry

EtOAc=ethyl acetate

EtOH=ethanol

HCl=hydrochloric acid

HOAc=acetic acid

K₂CO₃=potassium carbonate

KOAc=potassium acetate

LDA=lithium diisopropylamide

LC/MS=liquid chromatography—mass spectrometry

MeOH=methanol

MgSO₄=magnesium sulfate

MsCl=methanesulfonyl chloride or mesyl chloride

MW=microwave

NaBH₄=sodium borohydride

NaBH(OAc)₃=sodium triacetoxyborohydride

NaCNBH₃=sodium cyanoborohydride

NaHCO₃=sodium bicarbonate

NaOH=sodium hydroxide

Na₂S₂O₅=sodium metabisulfite or sodium pyrosulfite

NH₄OH=ammonium hydroxide

NMR=nuclear magnetic resonance

ON=overnight

Pd/C=palladium(0) on carbon

Pd(dppf)Cl₂=1,1′-bis(diphenylphosphino)ferrocenelpalladium(II) chloride

Pd(PPh₃)₄=tetrakis(triphenylphosphine)palladium(0)

Pd(PPh₃)₂Cl₂=bis(triphenylphosphine)palladium(II) dichloride

PE=petroleum ether

Pin₂B₂=bis(pinacolato)diboron

PPh₃=triphenylphosphine

PPTS=pyridinium p-toluenesulfonate

r.t.=room temperature

SEM-Cl=2-(trimethylsilyl)ethoxymethyl chloride

TEA=triethylamine

TFA=trifluoroacetic acid

THF=tetrahydrofuran

THP=tetrahydropyran

TLC=thin layer chromatography

p-TsOH=p-toluenesulfonic acid

The following example schemes are provided for the guidance of thereader, and collectively represent an example method for making thecompounds provided herein. Furthermore, other methods for preparingcompounds of the invention will be readily apparent to the person ofordinary skill in the art in light of the following reaction schemes andexamples. The skilled artisan is thoroughly equipped to prepare thesecompounds by those methods given the literature and this disclosure. Thecompound numberings used in the synthetic schemes depicted below aremeant for those specific schemes only, and should not be construed as orconfused with same numberings in other sections of the application.Unless otherwise indicated, all variables are as defined above.

General procedure

Compounds of Formula (I) of the present invention can be prepared asdepicted in Scheme 1.

Scheme 1 describes the method for preparation of1H-pyrazolo[3,4-b]Pyridine derivatives (VIII) by reacting5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde(II) with bis(pinacolato)diboron to form the borate ester (III). Suzukicoupling with various halides (IV) yields 1H-pyrazolo[3,4-b]pyridinederivatives (V). Aldehyde (V) is reacted with various 1,2-diamines (VI)to produce (VII). Final deprotection of the pyrazole nitrogen yields thedesired 1H-pyrazolo[3,4-b]pyridine derivatives (VIII).

Illustrative Compound Examples

Synthesis of intermediate5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde(XIX) is depicted below in Scheme 2.

Step 1

A solution of 2-chloropyridine (IX) (9.39 mL, 0.1mol) in anhydrous THF(50 mL) was added slowly to a solution of LDA (2.0 M solution inTHF/hexane/ethylbenzene, 50 mL, 0.1mol) in THF (200 mL) stirred at −78°C. under nitrogen. The stirring was continued at −78° C. for anadditional 3 h before adding acetaldehyde (6.17 mL, 0.110 mol). Thesolution was stirred at −78° C. for another 2 h before allowing thetemperature to rise to −40° C. A solution of water (4 mL) in THF (40 mL)was added slowly to the solution. When the temperature reached −10° C.,additional water (200 mL) was added to the solution. The solution wasextracted with ethyl ether (3×100 mL). The combined organic phase wasdried over MgSO_(4,) filtered and evaporated under reduced pressure toget a brown viscous residue. The crude product was purified on a flashsilica gel column (1:1DCM:hexane→100% DCM) to produce1-(2-chloropyridin-3-yl)ethanol (X) as a brown viscous oil (6 g,38.1mmol, 38% yield). ¹H NMR (CDCl₃) δppm 1.52 (d, J=6.41Hz, 3H),2.51(brs, 1H), 5.24 (m, 1H), 7.28 (m, 1H), 7.97 (dd, J=7.72 Hz, J=1.70Hz, 1H), 8.27 (dd, J=7.72 Hz, J=1.79 Hz, 1H).

Step 2

To a solution of 1-(2-chloropyridin-3-yl)ethanol (X) in dry acetone at−30° C. under nitrogen was added in portions chromium (VI) oxide (1.80g, 18 mmol). The solution was further stirred 15 min at −30° C. andallowed to warm to room temperature. The solution was stirred for 3 h atroom temperature before adding isopropanol (10 mL). The solution wasmade alkaline by slowly adding a saturated aqueous NaHCO3 solution. Thesolution was filtered through a bed of Celite. The solids were washed byDCM. The organic phase of the filtrate was separated and the aqueousphase extracted with DCM (2×50 mL). The combined organic layers weredried over MgSO4, filtered and concentrated under reduced pressure toyield 1-(2-chloropyridin-3-yl)ethanone (XI) as a brown liquid (0.72 g,4.63 mmol, 77% yield). ¹H NMR (CDCl₃) δppm 2.71(s, 3H), 7.35 (dd, J=7.63Hz, J=4.80 Hz, 1H), 7.91(dd, J=7.54 Hz, J=1.88 Hz, 1H), 8.55 (dd,J=4.71Hz, J=1.88 Hz, 1H).

Step 3

To a solution of 1-(2-chloropyridin-3-yl)ethanone (XI) (0.311g, 2 mmol)in n-butanol (10 mL) was added hydrazine hydrate (1.45 mL, 30 mmol). Thereaction was refluxed overnight. The solution was cooled and the solventwas evaporated under vacuum. The residue was dissolved in DCM and washedsuccessively by water and brine. The organic layers were dried overMgSO4, filtered and concentrated under reduced pressure to give3-methyl-1H-pyrazolo[3,4-b]pyridine (XII) as a white solid (192 mg, 1.44mmol, 72% yield). ¹H NMR (CDCl₃) δppm 2.64 (s, 3H), 7.14 (dd, J=8.01Hz,J=4.62 Hz, 1H), 8.14 (dd, J=7.54 Hz, J=1.88 Hz, 1H), 8.59 (dd, J=4.52Hz, J=1.32 Hz, 1H), 11.68 (brs, 1H).

Step 4

To a solution of NaOH (0.88 g, 22 mmol) in water (20 mL) was added3-methyl-1H-pyrazolo[3,4-b]pyridine (XII) (0.4 g, 3 mmol). Thesuspension was heated at 80° C. until a clear solution was obtained. Asolution of KMnO₄ (1.73 g, 11mmol) in water (180 mL) was added slowlyover 2 h while heating the solution at 80° C. The solution was heated at90° C. for an additional 2 h until the complete disappearance ofstarting material was observed by TLC. The solution was cooled to 70° C.and filtered through a pad of Celite. The solids were washed by boilingwater. The combined filtrate was cooled to 0° C., acidified with conc.H₂SO₄ to pH=2 and extracted with n-butanol (2×10 mL). The n-butanollayer was concentrated under reduced pressure to get a white residuewhich was dissolved in DCM by adding minimum amount of MeOH and thenfiltered. The filtrate was concentrated to give1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (XIII) as a white solid(390 mg, 2.39 mmol, 81% yield). ¹H NMR (CDCl₃) δppm 7.37 (dd, J=8.10 Hz,J=4.52 Hz, 1H), 8.47 (dd, J=7.54 Hz, J=1.88 Hz, 1H), 8.62 (dd, J=4.52Hz, J=1.32 Hz, 1H), 14.37 (brs, 1H).

Step 5

To a solution of 1H-pyrazole[3,4-b]pyridine-3-carboxylic acid (XIII)(0.39 g, 2.4 mmol) in dry MeOH (10 mL) was added concentrated H₂SO₄ (4drops) and refluxed for 6 h under nitrogen. The solution was cooled andthe solvent was evaporated under vacuum. The residue was partitionedbetween DCM and saturated aqueous NaHCO₃ solution. The organic layer wasseparated, dried over MgSO₄, filtered and concentrated under reducedpressure. The crude product was purified on a flash silica gel column(100% DCM→3:97 MeOH:DCM) to produce methyl1H-pyrazolo[3,4-b]pyridine-3-carboxylate (XIV) as a white solid (382 mg,2.16 mmol, 90% yield). ¹H NMR (CDCl₃) δppm 4.08 (s, 3H), 7.38 (m, 1H),8.63 (dd, J=8.10 Hz, J=1.51Hz, 1H), 8.72 (dd, J=4.62 Hz, J=1.41Hz, 1H);ESIMS found for C₈H₇N₃O₂ m/z 178.2 (M+H).

Step 6

A mixture of methyl 1H-pyrazolo[3,4-b]pyridine-3-carboxylate (XIV)(0.177 g, 1mmol), sodium acetate (0.492 g, 6 mmol) and bromine (0.308mL, 6 mmol) in glacial acetic acid (5 mL) was heated overnight at 120°C. in a sealed tube. The solution was cooled and poured into water. Thesolids formed were filtered, washed with water and dried at roomtemperature under vacuum. The crude product was purified on a flashsilica gel column (100% DCM→2:98 MeOH:DCM) to produce methyl5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylate (XV) as a white solid(78 mg, 0.31mmol, 30% yield). ¹H NMR (CDCl₃) δppm 3.95 (s, 3H), 8.62 (d,J=3.01Hz, 1H), 8.73 (d, J=3.01Hz, 1H); ESIMS found for C₈H₆BrN₃O₂m/z256.3 (M+H).

Step 7

A suspension of methyl 5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylate(XV) (70 mg, 0.27 mmol) in aqueous 1N NaOH solution (20 mL) was heatedat 90° C. for 3 h until the solution became clear. The solution was thencooled to 0° C. and acidified with a 10% HCl solution. The solids formedwere filtered, washed with cold water and dried at room temperatureunder vacuum to give 5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylicacid (XVI) as a white solid (60 mg, 0.25 mmol, 92% yield). ¹H NMR(CDCl₃) δppm 8.58 (d, J=3.01Hz, 1H), 8.66 (d, J=3.01Hz, 1H); ESIMS foundfor C₇H₄BrN₃O₂m/z 242.1(M+H).

Step 8

To a solution of 5-bromo-1H-pyrazole[3,4-b]pyridine-3-carboxylic acid(XVI) (0.242 g, 1mmol) in dry DMF (5 mL) was added CDI (0.178 g,1.1mmol) and heated for 3 h at 65° C. under nitrogen. The solution wascooled to room temperature and N,O-dimethyl hydroxylamine hydrochloride(0.107 g, 1.1mmol) was added to the solution. The solution was againheated for 3 h at 65° C. under nitrogen. The solution was cooled and thesolvent was evaporated under reduced pressure. The residue was dissolvedin DCM, washed successively with a 10% HCl solution, a saturated aqueousNaHCO₃ solution and brine. The organic phase was dried over MgSO₄,filtered and concentrated under reduced pressure to produce5-bromo-N-methoxy-N-methyl-1H-pyrazolo[3,4-b]pyridine-3-carboxamide(XVII) as a white solid (260 mg, 0.91mmol, 92% yield). ¹H NMR (CDCl₃)δppm 3.55 (s, 3H), 3.78 (s, 3H), 8.59 (d, J=3.01Hz, 1H), 8.67 (d,J=3.01Hz, 1H); ESIMS found for C₉H₉BrN₄O₂m/z 285.4 (M+H).

Step 9

To a solution of5-bromo-N-methoxy-N-methyl-1H-pyrazolo[3,4-b]pyridine-3-carboxamide(XVII) (0.250 g, 0.88 mmol) in dry DCM (10 mL) was added 3,4-dihydro-2H-pyran (0.179 mL, 1.98 mmol) and PPTS (22 mg, 0.08 mmol) and refluxed 5h under nitrogen. Another equivalent of 3,4-dihydro-2H-pyran (0.179 mL,1.98 mmol) and PPTS (22 mg, 0.08 mmol) was added and the solution wasfurther heated at refluxed overnight under nitrogen. The solution wascooled, diluted with DCM, washed subsequently with a saturated aqueousNaHCO₃ solution and brine. The organic layer was dried over MgSO_(4,)filtered and concentrated under reduced pressure to give5-bromo-N-methoxy-N-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamide(XVIII) as a viscous liquid (302 mg, 0.82 mmol, 93% yield). ¹H NMR(CDCl₃) δppm 1.51-1.62 (m, 2H), 1.91-2.13 (m, 2H), 2.33-2.44 (m, 2H),3.40 (s, 3H), 3.66 (m, 1H), 3.75 (s, 3H), 3.87-3.98 (m, 1H), 6.07 (dd,J=10.07 Hz, J=2.52 Hz, 1H), 8.57 (d, J=3.01Hz, 1H), 8.73 (d, J=3.01Hz,1H); ESIMS found for C₁₄H₁₇BrN₄O₃ m/z 369.4 (M+H).

Step 10

To a solution of5-bromo-N-methoxy-N-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamide(XVIII) (0.290 g, 0.78) in dry THF (5 mL) stirred at 0° C. undernitrogen was added lithium aluminum hydride (36 mg, 0.94 mmol). Thesolution was further stirred at 0° C. for 30 min. The reaction wasquenched with a 0.4 N NaHSO₄ solution (10 mL). The solution wasextracted with DCM (3×15 mL). The combined organic layer was washedsubsequently with water and brine. The organic layer was dried overMgSO_(4,) filtered and concentrated under reduced pressure to produce1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde(XIX) as a viscous liquid (218 mg, 0.70 mmol, 91% yield). ¹H NMR (CDCl₃)δppm 1.52-1.74 (m, 2H), 1.95-2.18 (m, 2H), 2.37-2.49 (m, 2H) 3.87-3.98(m, 1H), 3.99 (m, 1H), 6.18 (dd, J=10.20 Hz, J=2.39 Hz, 1H), 8.73 (d,J=3.01Hz, 1H), 8.85 (d, J=3.01Hz, 1H), 10.16 (s, 1H); ESIMS found forC₁₂H₁₂BrN₃O₂m/z 310.4 (M+H).

Preparation of intermediate N-(5-bromopyridin-3-yl)pivalamide (XXII) isdepicted below in Scheme 3.

Step 1

To a solution of 3-amino-5-bromo pyridine (XX) (1.0 g, 5.78 mmol) in drypyridine (10 mL) was added pivaloyl chloride (XXI) (769 mg, 6.38 mmol).The reaction mixture was stirred at room temperature for 3 h. Thereaction was poured into an ice water/saturated aqueous NaHCO₃ mixtureand stirred for 30 min. The precipitate was filtered, washed with coldwater and dried at room temperature to yieldN-(5-bromopyridin-3-yl)pivalamide (XXII) as an off -white solid (1.082g, 4.22 mmol, 73.1% yield). ¹H NMR (DMSO-d₆, 500 MHz) δppm 1.23 (s, 9H),8.37 (d, J=2 Hz, 1H), 8.39 (t, J=2 Hz, 1H), 8.80 (d, J=2 Hz, 1H), 9.58(brs, 1H); ESIMS found C₁₀H₁₃BrN₂O m/z 258.9 (Br⁸¹M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 3.

N-(5-Bromopyridin-3-yl)isobutyramide (XXIII): Off-white solid, (71%yield). ¹H NMR (CDCl₃) δppm 8.55-8.35 (m, 3H), 7.32 (s, 1H), 2.59-2.48(m, 1H), 1.28-1.27 (d, 6H); ESIMS found C₉H₁₁BrN₂O m/z 242.9 (Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)propionamide (XXIV): Off white solid (92% yield).¹H NMR (DMSO-d₆) δppm 1.09 (t, J=7.54 Hz, 3H), 2.36 (q, J=7.54 Hz, 2H),8.36 (m, 2H), 8.65 (d, J=2.07 Hz, 1H), 10.26 (s, 1H); ESIMS foundC₈H₉BrN₂O m/z 231.1(Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)butyramide (XXV): Yellow solid (2.1g, 8.64 mmol,88.8% yield). ¹H NMR (CD₃OD, 400 MHz) δppm 1.02 (t, J=7.2 Hz, 3H), 1.74(sxt, J=7.2 Hz, 2H), 2.40 (t, J=7.2 Hz, 2H), 8.35 (d, J=2 Hz, 1H), 8.46(t, J=2 Hz, 1H), 8.63 (d, J=2 Hz, 1H); ESIMS found C₉H₁₁BrN₂O m/z243.1(Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)pentanamide (XXVI): Yellow solid (2.0 g, 7.78mmol, 85.3% yield). ¹H NMR (CD₃OD, 400 MHz) δppm 0.98 (t, J=7.4 Hz, 3H),1.43 (sxt, J=7.4 Hz, 2H), 1.70 (quin, J=7.4 Hz, 2H), 2.43 (t, J=7.6 Hz,2H), 8.35 (s, 1H), 8.45 (d, J=2 Hz, 1H), 8.64 (d, J=2 Hz, 1H); ESIMSfound C₁₀H₁₃BrN₂O m/z 256.9 (Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)-3-methylbutanamide (XXVII): Off white solid,(67% yield), ¹H NMR (CDCl₃, 500 MHz) δppm 8.55-8.42 (m, 3H), 7.62 (s,1H), 2.31-2.18 (m, 3H), 1.02-1.01(d, J=6 Hz, 6H); ESIMS foundC₁₀H₁₃BrN₂O m/z 258.9 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)-3,3-dimethylbutanamide (XXVIII): Yellow solid(1.7 g, 6.27 mmol, 78.6% yield). ¹H NMR (CD₃OD, 400 MHz) δppm 1.10 (s,9H), 2.29 (s, 2H), 8.36 (d, J=1.6 Hz, 1H), 8.46 (d, J=2.0 Hz, 1H), 8.64(d, J=2.0 Hz, 1H); ESIMS found C₁₁H₁₅BrN₂O m/z 273.1((Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)-2-phenylacetamide (XXIX): White solid (2.5 g,8.59 mmol, 77.9% yield). ¹H NMR (CDCl₃, 400 MHz) δppm 3.76 (s, 2H),7.26-7.45 (m, 5H), 7.57 (brs, 1H), 8.33 (s, 1H), 8.37 (s, 2H); ESIMSfound C₁₃H₁₁BrN₂O m/z 292.8 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)benzamide (XXX): White solid (2.7 g, 9.74 mmol,60% yield). ¹H NMR (CDCl₃, 400 MHz) δppm 7.40-7.52 (m, 2H), 7.52-7.62(m, 1H), 7.86 (d, J=7.2 Hz, 2H), 8.39 (d, J=1.6 Hz, 1H), 8.46 (s, 1H),8.55 (d, J=1.6 Hz, 1H), 8.57 (d, J=2.0 Hz, 1H); ESIMS found C₁₂H₉BrN₂m/z 278.8 (Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)cyclopropanecarboxamide (XXXI): Off-white solid,(83% yield), ¹H NMR (CDCl₃, 500 MHz) δppm 8.46-8.39 (m, 3H), 7.54 (bs,1H), 1.56-1.50 (m, 1H), 1.13-1.07 (m, 2H), 0.96-0.90 (m, 2H); ESIMSfound for C₉H₉BrN2O m/z 240.9 (Br⁷⁹M+H).

N-(5-Bromopyridin-3-yl)cyclobutanecarboxamide (XXXII): Yellow solid(2.1g, 6.27 mmol, 86.6% yield). ¹H NMR (CD₃OD, 400 MHz) δppm 1.80-1.99(m, 1H), 1.99-2.15 (m, 1H), 2.16-2.30 (m, 2H), 2.30-2.45 (m, 2H),3.25-3.35 (m, 1H), 8.34 (d, J=2.0 Hz, 1H), 8.47 (s, 1H), 8.64 (d, J=2.0Hz, 1H); ESIMS found C₁₀H₁₁BrN2O m/z 257.1(Br⁸¹M+H).

N-(5-Bromopyridin-3-yl)cyclopentanecarboxamide (XXXIII): Yellow solid(1.9 g, 7.06 mmol, 80.2% yield). ¹H NMR (CD₃OD, 400 MHz) δppm 1.57-1.74(m, 2H), 1.74-1.91(m, 4H), 1.91-2.07 (m, 2H), 2.77-2.92 (m, 1H), 8.34(d, J=1.6 Hz, 1H), 8.45 (s, 1H), 8.65 (d, J=2.0 Hz, 1H); ESIMS foundC₁₁H₁₃BrN2O m/z 271.1(Br⁸¹M+H).

N-(5-bromopyridin-3-yl)cyclohexanecarboxamide (XXXIV): Yellow solid (2.0g, 7.06 mmol, 84.3% yield). ¹H NMR (CD₃OD, 400 MHz) δppm 1.19-1.46 (m,3H), 1.46-1.63 (m, 2H), 1.74 (d, J=11.6 Hz, 1H), 1.88 (t, J=14.0 Hz,4H), 2.40 (tt, J=11.6 Hz, J=3.6 Hz, 1H), 8.34 (d, J=2.0 Hz, 1H), 8.44(t, J=2.0 Hz, 1H), 8.64 (d, J=2.0 Hz, 1H); ESIMS found C₁₂H₁₅BrN₂O m/z285.1(Br⁸¹M+H).

N-(5-bromopyridin-3-yl)-2-cyclohexylacetamide (XXXV): Yellow solid (261mg, 0.878 mmol, 84.4% yield). ESIMS found C₁₃H₁₇BrN₂O m/z297.1(Br⁸¹M+H).

Preparation of intermediate 5-bromo-N,N-dimethylpyridin-3-amine (XXXVII)is depicted below in Scheme 4.

Step 1

To a solution of 3,5-dibromopyridine (XXXVI) (2.37 g, 10.0 mmol) in dryDMF (20.0 mL) was added K₂CO₃ (4.5 g, 33 mmol) and dimethylaminohydrochloride (1.79 g, 22 mmol). The mixture was heated overnight at200° C. in a sealed tube. The solution was cooled to room temperatureand excess DMF was removed under vacuum. The residue was partitionedbetween EtOAc and water. The organic phase was separated. The aqueousphase was washed with EtOAc and the combined organic phases were driedover MgSO₄, and concentrated to afford5-bromo-N,N-dimethylpyridin-3-amine (XXXVII) as an off-white solid(1.78g, 8.85 mmol, 88% yield). ¹H NMR (DMSO-d₆, 500 MHz) δppm 2.94 (s,6H), 7.25 (t, J=2 Hz, 1H), 7.91(d, J=2 Hz, 1H), 8.07 (d, J=2 Hz, 1H);ESIMS found C₇H₉BrN₂ m/z 201.1(M+H).

Preparation of intermediate 5-bromo-N-isopropylpyridin-3-amine (XXXVIII)is depicted below in Scheme 5.

Step 1

To a solution of 5-bromopyridin-3-amine (XX) (535 mg, 3.09 mmol) in MeOH(62 mL) was added acetone (296 μL, 4.02 mL). The pH was adjusted to 4using HOAc and stirred for 30 min. NaCNBH₃ (272 mg, 4.33 mmol) was addedand stirred at room temperature overnight. The MeOH was removed undervacuum and the residue was partitioned between EtOAc and saturatedaqueous NaHCO₃. The organic layer was dried over MgSO₄ and evaporatedunder vacuum. The crude product was purified on a silica gel column(100% hexane →90:10 hexane:EtOAc) to produce5-bromo-N-isopropylpyridin-3-amine (XXXVIII) as an oil which slowlysolidified into an off-white solid (309 mg, 1.44 mmol, 47% yield). ¹HNMR (DMSO-d₆, 500 MHz) δppm 1.12 (d, J=6.3 Hz, 6H), 3.55-3.59 (m, 1H),6.03 (d, J=7.9 Hz, 1H), 7.05-7.06 (m, 1H), 7.75 (d, J=2 Hz, 1H), 7.90(d, J=2 Hz, 1H); ESIMS found C₈H₁₁BrN₂ m/z 215.1(M+H).

Preparation of intermediate 1-(5-bromopyridin-3-yl)-N,N-dimethylmethanamine (XL) is depicted below in Scheme 6.

Step 1

Preparation of 1-(5-bromopyridin-3-yl)-N,N-dimethylmethanamine (XL) wasperformed following the procedure listed in Scheme 5, Step 1. Brown oil(1.20 g, 5.59 mmol, 45% yield). ¹H NMR (DMSO-d₆, 500 MHz) δppm 2.15 (s,6H), 3.43 (s, 2H), 7.94 (s, 1H), 8.47 (d, J=1.1Hz, 1H), 8.59 (d, J=2.2Hz, 1H); ESIMS found C₈H₁₁BrN₂ m/z 215 (M^(Br79)+H) and 217 (M^(Br81)+H)

Preparation of intermediate3-bromo-5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridine (XLI) isdepicted below in Scheme 7.

Step 1

To a mixture of 5-bromopyridine-3-carbaldehyde (XXXIX) (6.00 g, 32.26mmol, 1.0 eq), 3,3-difluoropyrrolidine (5.56 g, 38.71mmol, 1.20 eq) andTEA (5.39 mL,38.71mmol, 1.2 Eq) in DCE (200 mL) was stirred at roomtemperature for 30 min, then added sodium triacetoxyborohydride (10.25g, 48.38 mmol, 1.50 eq) in one portion at room temperature under N_(2.)The mixture was stirred at room temperature for 6 hours. TLC showed thereaction was complete. The reaction was quenched with 1N NaOH (100 mL),extracted with DCE (100 mL X 2). The combined organic layers were washedwith brine (100 mL), dried and concentrated. The residue was purified bysilica gel chromatography (column height: 50 mm, diameter: 50 mm,300-400 mesh silica gel, DCM/MeOH=30/1→20/1) to give3-bromo-5-((3,3-difluoropyrrolidin-1-yl)methyl) pyridine (XLI): Yellowoil (8.00 g, 28.9 mmol, 89.5% yield). ¹H NMR (CDCl₃, 400 MHz) δppm 2.30(spt, J=7.2 Hz. 2H), 2.75 (t, J=6.8 Hz, 2H), 2.91(t, J=13.2 Hz, 2H),7.85 (s, 1H), 8.45 (s, 1H), 8.59 (d, J=2 Hz, 1H); ESIMS found forC₁₀H₁₁BrF₂N₂ m/z 277.0 (M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 6 or Scheme 7.

3-Bromo-5-(pyrrolidin-1-ylmethyl)pyridine (XLI): Golden liquid (1.35 g,97% yield). ¹H NMR (DMSO-d₆) 1.68-1.71(m, 4H), 2.42-2.44 (m, 4H), 3.60(s, 2H), 7.96 (s, 1H), 8.48 (d, J=2 Hz, 1H), 8.58 (d, J=3 Hz, 1H); ESIMSfound for C₁₀H₁₃BrN₂ m/z 242.2 (M+H).

3-Bromo-5-(piperidin-1-ylmethyl)pyridine (XLII): Brown liquid (13.1g,94% yield). ¹H NMR (DMSO-d₆) 1.36-1.39 (m, 2H), 1.46-1.51(m, 4H),2.31-2.32 (m, 4H), 3.46 (s, 2H), 7.94 (s, 1H), 8.47 (d, J=2 Hz, 1H),8.58 (d, J=3 Hz, 1H); ESIMS found for C₁₁H₁₅BrN₂ m/z 257.0 (M+H).

N-((5-Bromopyridin-3-yl)methyl)ethanamine (XLIII): Golden liquid (1.29g, 6.00 mmol, 60% yield). ¹H NMR (CDCl₃, 400 MHz) δppm 1.14 (t, J=7.2Hz, 3H), 2.67 (q, J=7.2 Hz, 2H), 3.79 (s, 2H), 7.85 (t, J=2 Hz, 1H),8.46 (d, J=1.6 Hz, 1H), 8.56 (d, J=2.4 Hz, 1H); ESIMS found forC₈H₁₁BrN2 m/z 215.1(M+H).

N-Benzyl-1-(5-bromopyridin-3-yl)methanamine (XLIV): Yellow oil (8.0 g,28.9 mmol, 89.5% yield). ¹H NMR (DMSO-d₆, 400 MHz) δppm 3.71(s, 2H),3.74 (s, 2H), 7.18-7.28 (m, 1H), 7.28-7.40 (m, 4H), 8.04 (s, 1H), 8.52(s, 1H), 8.58 (s, 1H); ESIMS found for C₁₃H₁₃BrN₂ m/z 277.1(M+H).

Preparation of intermediatetert-butyl(5-bromopyridin-3-yl)methyl(cyclopentylmethyl)carbamate (L) isdepicted below in Scheme 8.

Step 1

To a solution of 5-bromonicotinaldehyde (XXXIX) (2.0 g, 10.8 mmol, 1eq)in MeOH (20 mL) was added NaBH₄ (2.4 g, 64.9 mmol, 6 eq) and thereaction mixture was stirred at room temperature for 3 h. The mixturewas concentrated in vacuo and the residue was diluted in water (15 mL),the aqueous phase was extracted with DCM (10 mL×3). The combined organiclayers were dried over MgSO4, filtered and concentrated in vacuo toafford (5-bromopyridin-3-yl)methanol (XLVI) (1.8 g, 9.57 mmol, 90.0%yield) as a colorless oil. ¹HNMR (CDCl₃, 500 MHz) δppm 4.73 (s, 2H),7.90 (s, 1H), 8.47 (s, 1H), 8.57 (s, 1H). ESIMS found for C₆H₆BrNO m/z188.0 (M+H).

Step 2

To a stirred solution of (5-bromopyridin-3-yl)methanol (XLVI) (1.60 g,8.5 mmol, 1eq), phthalimide (1.24 g, 8.5 mmol, 1eq) and PPh₃ (3.33 g,12.75 mmol, 1.5 eq) in anhydrous THF (15 mL) was added DEAD (2.21g,12.75 mmol, 1.5 eq) dropwise at 0° C. under N₂. Then the reactionmixture was stirred at room temperature for 6 h. The mixture was washedwith saturated NaHCO₃ solution (15 mL), water (15 mL) and brine (15 mL)subsequently. The organic layers were dried over MgSO_(4,) concentratedunder reduced pressure, the resultant residue was purified by flashchromatography on silica gel (PE:EtOAc=4:1) to give2-((5-bromopyridin-3-yl)methyl)isoindoline-1,3-dione (XLVII) (2.5 g,7.88 mmol, 82.3% yield) as a white solid. ESIMS found for C₁₄H9BrN₂O₂m/z 317.1(M+H).

Step 3

A solution of 2-((5-bromopyridin-3-yl)methyl)isoindoline-1,3-dione(XLVII) (1.9 g, 6.0 mmol, 1eq) and hydrazine hydrate (2.0 g, 40 mmol, 6eq) in EtOH (20 mL) was heated at 70° C. for 3 h. The mixture wasfiltered through a Celite® pad and the filtrate was concentrated invacuo, the crude product was dissolved in 1N HCl solution (15 mL) andconcentrated to dryness, then it was washed with acetone (10 mL×3), theprecipitate was collected by filtration, dried in vacuo to give(5-bromopyridin-3-yl)methanamine (XLVIII) (1.3 g, 6.95 mmol, 97.7%yield) as a white solid. ¹H NMR (D₂O, 500 MHz) δppm 4.34 (s, 2H), 8.56(s, 1H), 8.75 (d, J=1.2 Hz, 1H), 8.91(d, J=1.6 Hz, 1H). ESIMS found forC₆H₇BrN₂ m/z 187.0 (M+H).

Step 4

A solution of (5-bromopyridin-3-yl)methanamine (XLVIII) (1.30 g, 5.8mmol, 1.0 eq), cyclopentanecarbaldehyde (0.57 g, 5.8 mmol, 1.0 eq) andTEA (0.60 g, 5.8 mmol, 1.0 eq) in MeOH (15 mL) was stirred at roomtemperature for 2 h. Then NaBH₃CN (1.98 g, 34.6 mmol, 6.0 eq) was addedand the mixture was stirred at the same temperature for another 3 h. Thesolvent was removed under reduced pressure and the residue was dilutedin water (20 mL) and extracted with DCM (10 mL×3), combined organiclayers were dried over MgSO₄ and concentrated in vacuo to give1-(5-bromopyridin-3-yl)-N-(cyclopentylmethyl)methanamine (XLIX) (1.23 g,4.57 mmol, 79.3% yield) as a yellow oil. ¹H NMR (CDCl₃, 400 MHz) δppm1.07-1.23 (m, 2H), 1.47-1.67 (m, 4H), 1.70-1.84 (m, 2H), 2.02 (spt,J=7.6 Hz. 1H), 2.53 (d, J=7.2 Hz, 2H), 3.80 (s, 2H), 7.86 (s, 1H), 8.47(s, 1H), 8.56 (d, J=2.0 Hz, 1H); ESIMS found for C₁₂H₁₇BrN₂ m/z269.1(M+H).

Step 5

To a solution of1-(5-bromopyridin-3-yl)-N-(cyclopentylmethyl)methanamine (XLIX) (1.00 g,3.7 mmol, 1eq) and TEA (0.93 g, 9.2 mmol, 2.5 eq) in DCM (20 mL) wasadded portionwise (Boc)₂₀ (0.85 g, 4.0 mmol, 1.1eq) at 0° C., thereaction mixture was stirred at room temperature for 1h. The mixture waswashed with water (10 mL), brine (10 mL), the organic layer wasseparated, dried over MgSO₄ and concentrated in vacuo to give tert-butyl(5-bromopyridin-3-yl)methyl(cyclopentylmethyl)carbamate (L) (1.25 g,3.38 mmol, 91.9% yield) as a white solid. ESIMS found for C₁₇H₂₅BrN₂O₂m/z 369.1(M+H).

Preparation of intermediate 3-bromo-5-(cyclohexyloxy)pyridine (LIII) isdepicted below in Scheme 9.

Step 1

To a solution of 5-bromopyridin-3-ol (LI) (523 mg, 3.01mmol) in THF (30mL) cooled to 0° C. were added triphenylphosphine (867 mg, 3.31mmol) andcyclohexanol (LII) (331mg, 3.31mmol) followed by (E)-bis(4-chlorobenzyl)diazene-1,2-dicarboxylate (1.21g, 3.31mmol), added portionwise. Thereaction mixture was then stirred at 25° C. overnight. The reaction wasworked-up with a EtOAc-NaHCO₃ extraction and the solid filtered off Thesolvent was removed and the residue was purified by Isco (20%EtOAc-Hexanes) to give 3-bromo-5-(cyclohexyloxy)pyridine (LIII) (209 mg,0.82 mmol, 27.2% yield) as a yellow oil. ¹H NMR (DMSO-d₆, 500 MHz) δppm1.21-1.31(m, 1H) 1.34-1.48 (m, 4H) 1.49-1.57 (m, 1H) 1.70 (br dd,J=9.74, 4.25 Hz, 2H) 1.88-1.96 (m, 2H) 2.50 (dt, J=3.70, 1.72 Hz, 5H)4.46-4.54 (m, 1H) 7.72 (t, J=2.20 Hz, 1H) 8.24 (d, J=1.92 Hz, 1H) 8.27(d, J=2.47 Hz, 1H).

The following intermediate was prepared in accordance with the proceduredescribed in the above Scheme 9.

tert-Butyl 4-((5-bromopyridin-3-yl)oxy)piperidine-1-carboxylate (L):Yellow oil (244 mg, 0.683 mmol, 23.2% yield). ESIMS found forC₁₅H₂₁BrN₂O₃ m/z 358.3 (M+H).

Preparation of intermediate 3-(benzyloxy)-5-bromopyridine (LVI) isdepicted below in Scheme 10.

Step 1

To a solution of 5-bromopyridin-3-ol (LI) (174 mg, 1.0 mmol) in DMF (3mL) was added potassium carbonate (415 mg, 3.0 mmol). The slurry washeated at 90° C. for 1hour and then cooled to 25° C. The(bromomethyl)benzene (LV) (171mg, 1.0 mmol) was added and the mixturewas stirred at 25° C. overnight. The reaction was worked-up using asaturated sodium bicarbonate and ethyl acetate extraction. The productwas purified by ISCO column eluted with 40-100% EtOAc-Hexanes. The3-(benzyloxy)-5-bromopyridine (LVI) (105 mg, 0.398 mmol, 39.8% yield)was obtained as yellow oil. MS: 266.1. ESIMS found for C12H₁₀BrNO m/z266.1(M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 10.

3-Bomo-5-(2-(pyrrolidin-1-yl)ethoxy)pyridine (LVII): Yellow oil ((97 mg,0.358 mmol, 15.56% yield). ESIMS found for C₁₁H₁₅BrN2O m/z 272.2 (M+H).

2-((5-bromopyridin-3-yl)oxy)-N,N-dimethylethan-1-amine (LVIII): Yellowoil (97 mg, 0.396 mmol, 28.9% yield). ESIMS found for C₉H₁₃BrN₂O m/z245.1(M+H).

1-(2-(3-bromo-5-fluorophenoxy)ethyl)pyrrolidine (LIX): Yellow oil (370mg, 1.284 mmol, 85.8% yield). ESIMS found for C₁₂H₁₅BrFNO m/z 289.0(M+H).

2-(3-bromo-5-fluorophenoxy)-N,N-dimethylethan-1-amine (LX): Yellow oil(364 mg, 1.389 mmol, 50.2% yield). ESIMS found for C₁₀H₁₃BrFNO m/z 263.9(M+H).

Preparation of intermediate tert-butyl4-(2-((5-bromopyridin-3-yl)amino)-2-oxoethyl)piperidine-1-carboxylate(LXII) is depicted below in Scheme 11.

Step 1

To a solution of 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)acetic acid(LXI) (3.4 g, 13.97 mmol) in DCM (10 mL) was added DMF (1mL). Thesolution was cooled in ice -water to 0° C. Oxalyl chloride (1.835 mL,20.96 mmol) was then added dropwise. The mixture was stirred for onehour at 25° C. The organic volatile was then removed under vacuum. Theresidue was dissolved in DCM (10 mL). DMAP (0.171g, 1.397 mmol) and5-bromopyridin-3-amine (XX) (2.418 g, 13.97 mmol) were added to thesolution and cooled to 0° C. DIEA (4.88 ml, 27.9 mmol) was then addeddropwise and the mixture was stirred for 2 hours at 25° C. The reactionwas worked -up with DCM and saturated NaHCO3. The product was purifiedby ISCO eluted with 0-100% EtOAc-Hexanes. The tert-butyl4-(2-((5-bromopyridin-3-yl)amino)-2-oxoethyl)piperidine-1-carboxylate(LXII) (2.82 g, 7.08 mmol, 50.7% yield) was obtained as yellow oil.ESIMS found for C₁₇H2-(BrN₃O₃ m/z 343.1(M-56).

The following intermediate was prepared in accordance with the proceduredescribed in the above Scheme 11.

N-(5-Bromopyridin-3-yl)-2-(dimethylamino)acetamide (LXIII): Yellow oil(528 mg, 2.05 mmol, 19.0% yield). ESIMS found for C₉H₁₂BrN₃O m/z 259.3(M+H).

Preparation of tert-butyl(1-(6-chloropyrazin-2-yl)azetidin-3-yl)carbamate

(LXVI) is depicted below in Scheme 12.

Step 1

To a solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (LXIV)(2 g, 9.58 mmol) in dry DMF (19.2 mL) was added DIPEA (8.37 ml, 47.9mmol). To this mixture was added 2,6-dichloropyrazine (LXV) (1.428 g,9.58 mmol) and the reaction was stirred at 95° C. for 3 hours. Thereaction was quenched with water (20 mL) and extracted with EtOAc. Theorganic layer was dried over anhydrous Na₂SO_(4,) filtered andconcentrated. The residue was purified by silica gel columnchromatography (40g) (100% hexanes→hexanes:EtOAc 1:1) to yieldtert-butyl (1-(6-chloropyrazin-2-yl)azetidin-3-yl)carbamate (LXVI)(2.2882 g, 8.04 mmol, 83.9% yield) as a white solid. ESIMS found forC₁₂H₁₇CIN₄O₂ m/z 285.1(M+H).

Preparation of intermediate 2-(3-fluorophenyl)pyridine-3,4-diamine (LXX)is depicted below in Scheme 13.

Step 1

A solution of 2-chloro-3-nitropyridin-4-amine (LXVII) (2.0 g, 11.5 mmol,1.0 eq), (3-fluorophenyl)boronic acid (LXVIII) (1.93 g, 13.8 mmol, 1.2eq), Pd(PPh₃)₄ (0.40 g, 0.34 mmol, 0.03 eq), Na₂CO3 (2.44 g, 23.05 mmol,2.0 eq) in a mixed solvent of toluene (20 mL), H₂O (10 mL) and EtOH (4mL) was stirred at 75° C. for 15 h under nitrogen atmosphere. Then thereaction mixture was washed with brine (30 mL) and dried over anhydrousNa₂SO_(4,) filtered and concentrated in vacuo, the resultant residue waspurified by chromatography on silica gel (PE:EtOAc=1:1) to afford2-(3-fluorophenyl)-3-nitropyridin-4-amine (LXIX) (1.91g, 8.2 mmol, 71.2%yield) as a yellow solid. ESIMS found for C₁₁H₈FN₃O₂ m/z 234.2 (M+H).

Step 2

To a solution of 2-(3-fluorophenyl)-3-nitropyridin-4-amine (LXIX)(1.91g, 8.19 mmol, 1.0 eq) in MeOH (100 mL) was added Pd/C (0.8 g) undernitrogen atmosphere. The mixture was stirred under 50 psi of H₂ for 6 hat room temperature. The mixture was then filtered and concentrated invacuo to afford 2-(3-fluorophenyl)pyridine-3,4-diamine (LXX) as a blacksolid (1.52 g, 7.48 mmol, 91.3% yield). ¹H NMR (DMSO-d₆, 400 MHz) δppm4.30 (s, 2H), 5.55 (s, 2H), 6.44 (d, J=4.8 Hz, 1H), 7.07-7.19 (m, 1H),7.33 (dd, J=4.4 Hz, J=2 Hz, 1H), 7.38-7.49 (m, 2H), 7.57 (d, J=4.8 Hz,1H); ESIMS found C₁₁H₁₀FN₃ m/z 204.0 (M+H).

The following intermediates were prepared in accordance with theprocedure described in the above Scheme 13.

2-(4-Fluorophenyl)pyridine-3,4-diamine (LXXI): White Solid (1.56 g, 7.67mmol, 92.0% yield). ¹H NMR (CDCl₃, 400 MHz) 3.38 (brs, 2H), 4.02 (brs,2H), 6.57 (d, J=4.8 Hz, 1H), 7.15 (t, J=4.8 Hz, 2H), 7.59 (dd, J=8.4 Hz,J=5.6 Hz, 2H), 7.94 (d, J=5.2 Hz, 1H); ESIMS found for C₁₁H₁₀FN₃ m/z204.0 (M+H).

2-(2-Fluorophenyl)pyridine-3,4-diamine (LXXII): Yellow Solid (1.45 g,7.14 mmol, 89.2% yield). ¹NMR (CDCl₃, 400 MHz) 3.23 (brs, 2H), 4.12(brs, 2H), 6.62 (d, J=4.89 Hz, 1H), 7.19 (t, J=9.03 Hz, 1H), 7.24-7.33(m, 1H), 7.42 (d, J=6.02 Hz, 1H), 7.45-7.61(m, 1H), 8.00 (d, J=4.89 Hz,1H); ESIMS found for C₁₁H₁₀FN₃ m/z 204.0 (M+H).

[2,3′-Bipyridine]-3,4-diamine (LXXIII): Black Solid (1.19 g, 6.39 mmol,86.4% yield). ESIMS found for C₁₀H₁₀N₄ m/z 187.1(M+H).

2-(Thiophen-3-yl)pyridine-3,4-diamine (LXXIV): Yellow oil (1.12 g, 5.86mmol, 96.7% yield). ¹H NMR (CDCl₃, 400 MHz) 3.53 (brs, 2H), 3.99 (brs,2H), 6.55 (d, J=5.14 Hz, 1H), 7.40-7.49 (m, 2H), 7.56-7.62 (m, 1H), 7.93(d, J=5.14 Hz, 1H); ESIMS found for C₉H₉N₃S m/z 192.0 (M+H).

2-(Furan-3-yl)pyridine-3,4-diamine (LXXV): Yellow oil (1.32 g, 7.53mmol, 95.2% yield). ESIMS found for C₉H₉N₃O m/z 176.0 (M+H).

2-(Thiophen-2-yl)pyridine-3,4-diamine (LXXVI): Yellow oil (1.04 g, 5.44mmol, 98.3% yield). ¹H NMR (CDCl₃, 400 MHz) 3.22 (brs, 2H), 4.11(brs,2H), 6.61(d, J=4.8 Hz, 1H), 7.18 (t, J=9.0 Hz, 1H), 7.50 (d, J=6.8 Hz,1H), 7.44-7.58 (m, 1H), 7.99 (d, J=4.8 Hz, 1H); ESIMS found for C₉H₉N₃Sm/z 192.0 (M+H).

2-(5-Fluorothiophen-2-yl)pyridine-3,4-diamine (LXXVII): Yellow oil (1.2g, 5.74 mmol, 91.5% yield). ESIMS found for C₉H₈FN₃S m/z 210.1(M+H).

2-(5-Methylthiophen-2-yl)pyridine-3,4-diamine (LXXVIII): Yellow oil(1.20 g, 5.85 mmol, 86.0% yield). ¹H NMR (CD₃OD, 400 MHz) 2.55 (s, 3H),6.62 (d, J=6 Hz, 1H), 6.87 (d, J=1.2 Hz, 1H), 7.23 (d, J=3.2 Hz, 1H),7.63 (d, J=5.6 Hz, 1H); ESIMS found for C₁₀H₁₁N₃S m/z 206.0 (M+H).

1-(5-(3,4-Diaminopyridin-2-yl)thiophen-2-yl)ethan-1-one (LXXIX): Yellowoil (1.20 g, 5.85 mmol, 86.0% yield). ¹H NMR (DMSO-d₆, 400 MHz) 2.52 (s,3H), 4.84 (s, 2H), 5.83 (s, 2H), 6.46 (d, J=4.8 Hz, 1H), 7.57 (d, J=4.8Hz, 1H), 7.66 (d, J=4 Hz, 1H), 7.88 (d, J=4 Hz, 1H); ESIMS found forC₁₁H₁₁N₃OS m/z 234.0 (M+H).

3-(3,4-Diaminopyridin-2-yl)-5-fluorophenol (LXXX): White solid (320 mg,1.46 mmol, 84.6% yield). ESIMS found for C₁₁H₁₀FN₃O m/z 220.1(M+H).

2-(3-Fluoro-5-methoxyphenyl)pyridine-3,4-diamine (LXXXI): White solid(501mg, 2.148 mmol, 93.1% yield). ESIMS found for C₁₂H₁₂FN₃O m/z234.1(M+H).

2-(3-Fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)pyridine-3,4-diamine(LXXXI): Black oil (167 mg, 0.528 mmol, 80.9% yield). ESIMS found forC₁₇H₂₁FN₄ m/z 317.1(M+H).

2-(3-(2-(Dimethylamino)ethoxy)-5-fluorophenyl)pyridine-3,4-diamine(LXXXII): Black oil (88 mg, 0.303 mmol, 20.83% yield). ¹H NMR (DMSO-d₆,400 MHz) ; ESIMS found for C₁₅H₁₉FN₄ m/z 291.1(M+H).

Preparation of intermediate [2,4′-bipyridine]-3,4-diamine (LXXXVI) isdepicted below in Scheme 14.

Step 1

To a solution of pyridin-4-ylboronic acid (LXXXIV) (2.00 g, 16.3 mmol),2-chloro-3-nitropyridin-4-amine (LXVII) (2.35 g, 13.6 mmol), Na₂CO₃(5.03 g, 47.5 mmol) and Pd(dppf)Cl₂ (502.87 mg, 677.92 μmol in dioxane(40 mL) and H₂O (8 mL) was de-gassed and then heated to 80° C. overnightunder N_(2.) TLC (100% EtOAc) showed the starting material was consumedcompletely. The reaction mixture was poured into H₂O (300 mL). Themixture was extracted with EtOAc (3×250 mL). The organic phase waswashed with brine (300 mL), dried over anhydrous MgSO₄, concentrated invacuum to give a residue, which was purified by silica gel columnchromatography (DCM/MeOH=20/1) to afford3-nitro-[2,4′-bipyridin]-4-amine (LXXXV) (1.60 g, 7.4 mmol, 54.6% yield)as yellow solid. ESIMS found for C₁₀H₈N₄O₂ m/z 217.1(M+H).

Step 2

To a solution of 3-nitro-[2,4′-bipyridin]-4-amine (LXXXV) (1.60 g, 7.4mmol) in MeOH (30 mL), was added Fe (1.65 g, 29.6 mmol) and NH₄Cl (3.10g, 59.2 mmol) in one portion at rt. The mixture was stirred at rt. for10 min. Then heated to 80° C. and stirred for 16 hours. TLC showed thereaction was completed. The mixture was cooled to rt. and concentratedin reduced pressure at 60° C. The combined organic phase was washed withsaturated brine (100 mL×2), dried over anhydrous Na₂SO_(4,) filtered andconcentrated in vacuo. The to give crude [2,4′-bipyridine]-3,4-diamine(LXXXVI) (1.20 g, 6.44 mmol, 87.1% yield) as a yellow solid. ¹H NMR(DMSO-d₆, 400 MHz) 4.52 (s, 2H), 5.69 (s, 2H), 6.50 (d, J=4.8 Hz, 1H),7.62 (d, J=6 Hz, 2H), 7.63 (d, J=4.8 Hz, 1H), 8.61(d, J=6 Hz, 2H); ESIMSfound for C₁₀H₁₀N₄ m/z 187.0 (M+H).

Preparation of intermediate [2,2′-bipyridine]-3,4-diamine (LXXXIX) isdepicted below in Scheme 15.

Step 1

To a solution of 2-(tributylstannyl)pyridine (LXXXVII) (9.00 g, 24.5mmol, 1.0 eq), 2-chloro-3-nitropyridin-4-amine (LXVII) (4.24 g, 24.5mmol, 1.0 eq), Pd(PPh₃)₄ (28.25 g, 24.5 mmol, 1.0 eq) in dioxane (40 mL)was de-gassed and then heated to 100° C. for 1h under N_(2.) LC/MSshowed that half of the starting material was consumed. The mixture wasfiltered and concentrated in vacuum to give a residue, which waspurified by prep-HPLC (Base) to afford the3-nitro-[2,2′-bipyridin]-4-amine (LXXXVIII) (0.70 g, 3.24 mmol, 13.2%yield) as a light yellow oil. ESIMS found for C₁₀H₈N₄O₂ m/z 217.1(M+H).

Step 2

To a solution of 3-nitro-[2,2′-bipyridin]-4-amine (LXXXVIII) (700 mg,3.24 mmol, 1.0 eq) in MeOH (15 mL) was added Pd/C (200 mg, 3.24 mmol,1.0 eq). The mixture was stirred at 25° C. for 4 h. LC/MS showed thatthe starting material was completely consumed. The mixture was filteredand concentrated to give [2,2′-bipyridine]-3,4-diamine (LXXXIX) (450.0mg, 2.42 mmol, 74.6% yield) as a light brown solid. ¹H NMR (DMSO-d₆, 400MHz) 5.73 (brs, 2H), 6.52 (d, J=4.8 Hz, 1H), 6.76 (brs, 2H), 7.31(dt,J=5.6 Hz, J=1.2 Hz, 1H), 7.52-7.58 (m, 1H), 7.82 (dt, J=8 Hz, J=1.2 Hz,1H), 8.44 (d, J=8 Hz, 1H), 8.60 (d, J=6 Hz, 1H); ESIMS found forC₁₀H₁₀N₄ m/z 187.1(M+H).

Preparation of intermediate 2-(piperidin-1-yl)pyridine-3,4-diamine (XCI)is depicted below in Scheme 16.

Step 1

To a solution of 2-chloro-3-nitropyridin-4-amine (LXVII) (4.00 g, 23.5mmol, 1.0 eq) and piperidine (5.89 g, 69.1mmol, 3.0 eq) in DMF (60 mL)was added K₂CO₃ (9.56 g, 69.1mmol, 3.0 eq) in one portion and themixture was stirred at 120° C. under nitrogen overnight. The reactionmixture was diluted with EtOAc (30 mL) and washed with aqueous saturatedNaHCO₃ solution (80 mL). The organic phases were dried over Na₂SO₄ andconcentrated in vacuo, the resultant residue was purified by silica gelcolumn chromatography (PE:EtOAc=5:1→1:1) to give3-nitro-2-(piperidin-1-yl)pyridin-4-amine (XC) (3.87g, 5.42 mmol, 75.6%yield) as a black oil. ESIMS found for C₁₀H₁₄N₄O₂ m/z 223.1(M+H).

Step 2

A mixture of 3-nitro-2-(piperidin-1-yl)pyridin-4-amine (XC) (3.87g, 5.42mmol, 1.0 eq) and Pd/C (0.80 g) in MeOH (20 mL) was stirred at roomtemperature under 50 psi H₂ overnight. After the starting material wasconsumed completely, the mixture was filtered through a Celite pad andthe filtrate was concentrated in vacuo to give the2-(piperidin-1-yl)pyridine-3,4-diamine (XCI) (2.63 g, 13.7 mmol, 78.5%yield) as a black solid. ESIMS found C₁₀H₁₆N₄ m/z 193.0 (M+H).

Preparation of intermediate2-(4-methyl-1H-imidazol-1-yl)pyridine-3,4-diamine (XCV) is depictedbelow in Scheme 17.

Step 1

A solution of 2-methyl-3-nitropyridin-4-amine (XCII) (1.00 g, 5.76 mmol,1.0 eq), 4-methyl-1H-imidazole (XCIII) (0.94 g, 11.5 mmol, 2.0 eq) inDMF (10 mL) was stirred at 80° C. for 3h under microwave irradiation.The reaction was then quenched by water (15 mL). The mixture wasextracted with EtOAc (20×3), the organic layer were combined, washedwith brine (20 mL), dried over anhydrous Na₂SO_(4,) filtered andconcentrated in vacuo, the resultant residue was purified bychromatography on silica gel (PE:EtOAc=5:1→3:1) to afford2-(4-methyl-1H-imidazol-1-yl)-3-nitropyridin-4-amine (XCIV) (700 mg,3.19 mmol, 56.1% yield) as a yellow solid. ¹H NMR (DMSO-d₆, 400 MHz)δppm 2.13 (s, 3H), 6.88 (d, J=6 Hz, 1H), 7.03 (s, 1H), 7.54 (brs, 2H),7.82 (s, 1H), 8.01(d, J=5.6 Hz, 1H); ESIMS found for C₉H₉N₅O₂ m/z220.1(M+H).

Step 2

To a solution of 2-(4-methyl-1H-imidazol-1-yl)-3-nitropyridin-4-amine(XCIV) (700 mg, 3.19 mmol, 1.0 eq) in MeOH (20 mL) was added Pd/C (0.3g) under a nitrogen atmosphere. The mixture was stirred under 50 psi ofH₂ for 12 h at room temperature. The mixture was the filtered andconcentrated in vacuo to afford2-(4-methyl-1H-imidazol-1-yl)pyridine-3,4-diamine (XCV) (500 mg, 2.64mmol, 82.7% yield) as a white solid. ¹H NMR (DMSO-d₆, 400 MHz) 2.17 (s,3H), 4.36 (brs, 2H), 5.86 (brs, 2H), 6.51(d, J=5.2 Hz, 1H), 7.14 (s,1H), 7.43 (d, J=5.2 Hz, 1H), 7.77 (s, 1H); ESIMS found C₉H₁₁N₅ m/z190.1(M+H).

Preparation of intermediate2-(4-methylpiperazin-1-yl)pyridine-3,4-diamine (XCVIII) is depictedbelow in Scheme 18.

Step 1

A mixture of 1-methylpiperazine (XCVI) (20 mL) and2-chloro-3-nitropyridin-4-amine (LXVII) (4.0 g, 23.1mmol, 1.0 eq) wasstirred at 50° C. for 1h under microwave irradiation. The reactionmixture was diluted with water (100 mL) and filtered, the cake waswashed with water (30×3), dried in vacuo to give2-(4-methylpiperazin-1-yl)-3-nitropyridin-4-amine (XCVII) (4.0 g, 16.9mmol, 73.2% yield) as a yellow solid. ESIMS found for C₁₀H₁₅N₅O₂ m/z238.1(M+H).

Step 2

A mixture of 2-(4-methylpiperazin-1-yl)-3-nitropyridin-4-amine (XCVII)(4.0 g, 16.9 mmol, 1.0 eq) and Pd/C (0.5 g) in MeOH (200 mL) was stirredunder 50 psi of H2 at room temperature overnight. The reaction wasmonitored by TLC. The mixture was filtered and the filtrate wasconcentrated in vacuo to give2-(4-methylpiperazin-1-yl)pyridine-3,4-diamine (XCVIII) (3.13 g, 89.6%yield) as a black solid. ¹H NMR (DMSO-d₆, 400 MHz) 2.74 (s, 4H), 3.12(s, 3H), 3.44 (brs, 4H), 5.19 (brs, 4H), 6.60 (d, J=6.4 Hz, 2H); ESIMSfound C₁₀H₁₇N₅ m/z 208.1(M+H).

Preparation of intermediateN-(3-(3,4-diaminopyridin-2-yl)-5-fluorobenzyl)methanesulfonamide (CIV)is depicted below in Scheme 19.

Step 1

A solution of 3-bromo-5-fluorobenzonitrile (XCIX) (44.0 g, 220.0 mmol,1.0 eq) was dissolved in THF (30 mL). BH₃—Me₂S (33.43 g, 440.0 mmol, 2.0eq) was added to the solution at 20° C. Then it was stirred at 80° C.for 2 h, HCl (6 N, 100 mL) was added to the mixture slowly at 20° C. Themixture was stirred at 80° C. for 1h, then it was washed with EtOAc (300ml). The water phase was basified with 50% aqueous NaOH and it wasextracted with EtOAc (300 mL×3). The combined organic layers were driedover anhydrous Na₂SO₄ and concentrated in vacuo to produce(3-bromo-5-fluoro-phenyl)methanamine (C) (24.0 g, 117.62 mmol, 53.5%yield). ¹H NMR NMR (CDCl₃, 300 MHz) 3.86 (s, 2H), 7.01(d, J=8 Hz, 1H),7.12 (d, J=8 Hz, 1H), 7.28 (s, 1H); ESIMS found C₇H₇BrFN m/z 203.9(Br⁷⁹M+H).

Step 2

A solution of (3-bromo-5-fluoro-phenyl)methanamine (C) (23.0 g, 112.7mmol, 1.0 eq) was dissolved in DCM (15 mL), TEA (34.22 g, 338.2 mmol,3.0 eq) was added to the mixture. Then MsCl (13.44 g, 117.3 mmol, 1.04eq) was added slowly to the solution at 0° C. It was stirred at 0-30° C.for 2 h. The reaction was washed with water and extracted with EtOAc.The combined organic layers were dried over anhydrous Na₂SO₄ andconcentrated to give N-(3-bromo-5-fluorobenzyl)methanesulfonamide (CI)(34.0 g, 102.44 mmol, 90.9% yield, 85% purity) as an oil. ¹H NMR (CDCl₃,300 MHz) 2.88 (s, 3H), 4.24 (d, J=4.5 Hz, 2H), 6.99 (d, J=9 Hz, 1H),7.13 (dt, J=8.1Hz, J=2 Hz, 1H), 7.25 (s, 1H); ESIMS found C₈H₉BrFNO₂Sm/z 282.0 (Br⁷⁹M+H).

Step 3

A solution of N-(3-bromo-5-fluorobenzyl)methanesulfonamide (CI) (34.0 g,102.4 mmol, 1.0 eq) and4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane(52.02 g, 204.9 mmol, 2.0 eq), KOAc (20.11g, 204.9 mmol, 2.0 eq) wasdissolved in dioxane (20 mL). Then Pd(dppf)Cl₂ (7.60 g, 10.2 mmol,0.1eq) was added to the mixture. It was stirred at 90° C. for 2 h. Thenthe solvent was removed to get the residue which was purified by silicagel column (PE:EtOAc ═10:1→100% EtOAc) to getN-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)methanesulfonamide(CII) (30.0 g, crude). ¹H NMR (CDCl₃, 400 MHz) 1.37 (s, 12H), 2.92 (s,3H), 4.34 (d, J=6.3 Hz, 2H), 7.19 (dt, J=9.3 Hz, J=2.1Hz, 1H), 7.44 (dd,J=8.7 Hz, J=2.4 Hz, 1H), 7.54 (s, 1H); ESIMS found C₁₄H₂₁BFNO₄S m/z330.1(M+H).

Step 4

A solution ofN-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)methanesulfonamide(CII) (5.00 g, 15.19 mmol, 1.0 eq) and 2-chloro-3-nitropyridin-4-amine(LXVII) (2.64 g, 15.19 mmol, 1.0 eq), Cs₂CO₃ (9.90 g, 30.4 mmol, 2.0 eq)was dissolved in dioxane (40 mL) and water (8 mL). Then Pd(dppf)Cl₂(1.13 g, 1.52 mmol, 0.1eq) was added to the mixture. The mixture wasstirred at 100° C. for 10 h under N2. The solvent was removed to get theresidue which was purified by silica column to getN-(3-(4-amino-3-nitropyridin-2-yl)-5-fluorobenzyl)methanesulfonamide(CIII) (3.00 g, 8.81mmol, 58.0% yield) as an oil. ESIMS foundC₁₃H₁₃FN₄O₄S m/z 341.1(M+H).

Step 5

A solution ofN-[[3-(4-amino-3-nitro-2-pyridyl)-5-fluoro-phenyl]methyl]methanesulfonamide(CIII) (3.00 g, 8.8 mmol, 1.0 eq), Fe (2.46 g, 44.1mmol, 5.0 eq) andNH₄Cl (2.36 g, 44.1mmol, 5.0 eq) was dissolved in MeOH (35 mL). Themixture was stirred at 80° C. for 2 h. After filtration, the filtratewas concentrated to getN-(3-(3,4-diaminopyridin-2-yl)-5-fluorobenzyl)methanesulfonamide (CIV)(2.20 g, 7.09 mmol, 80.5% yield) as black solid. ¹H NMR NMR (CDCl₃, 400MHz) 2.96 (s, 3H), 4.28 (d, J=6 Hz, 2H), 5.33 (brs, 2H), 6.81(d, J=6.5Hz, 1H), 7.38-7.40 (m, 2H), 7.75 (d, J=6.5 Hz, 1H); ESIMS foundC₁₃H₁₅FN₄O₂S m/z 311.1(M+H).

Preparation of intermediate5-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)pyridine-3,4-diamine(LXXXIX) is depicted below in Scheme 20.

Step 1

A solution of 3-bromo-5-fluorobenzaldehyde (CV) (20.0 g, 98.2 mmol, 1.0eq) in MeOH (1.8 L) was added N¹,N¹-dimethylethane-1,2-diamine (21.5 mL,196.4 mmol, 2.0 eq). The pH was adjusted to 6 using HOAc and stirred for1h. NaCNBH₃ (8.6 g, 137.5 mmol, 1.4 eq) was added and stirred at roomtemperature overnight. The MeOH was removed under vacuum and the residuewas partitioned between CHCl₃ and saturated aqueous NaHCO_(3.) Theorganic layer was dried over MgSO₄ and evaporated under vacuum. Thecrude product was purified on a silica gel column (100% CHCl₃→3:97MeOH[7N NH₃]:CHCl₃) to produceN¹-(3-bromo-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine (CVI) as ayellow oil (13.0 g, 49.9 mmol, 51% yield). ¹HNMR (DMSO-d₆, 500 MHz) δppm1.28 (s, 6H), 2.39 (t, J=4 Hz, 2H), 3.07 (q,J=6 Hz, 2H), 6.10 (t, J=5Hz, 1H), 6.38 (td, J=12 Hz, J=2 Hz, 1H), 6.51(td, J=8.6 Hz, J=2 Hz, 1H),6.61(t, J=2 Hz, 1H); ESIMS found C₁₀H₁₄BrFN₂ m/z 261.0 (M+H).

Step 2

A solution ofN¹-(3-bromo-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine (CVI) (13.0g, 49.9 mmol, 1.0 eq), bis(pinacolato)diboron (12.6 g, 59.9 mmol, 1.2eq), KOAc (12.1g, 124.3 mmol, 2.5 eq) and dioxane (600 mL) was purgedwith argon. Pd(dppf)Cl₂ (2.0 g, 2.47 mmol, 0.05 eq) was added to thereaction and purged again with argon. The solution was heated at 90° C.for 2 h. Once TLC showed the disappearance of (CVI), the solution wascooled to room temperature and then concentrated under reduced pressureto produce crude N¹-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(CVII) (7.4 g, 24.0 mmol, 48.2% yield).

Step 3

To a solution ofN¹-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine(CVII) (2.00 g, 6.49 mmol, 1.2 eq), 2-bromo-3-nitropyridin-4-amine(CVIII) (1.18 g, 5.41mmol, 1.0 eq), Na₂CO₃ (1.15 g, 10.82 mmol, 2.0 eq)and Pd(dppf)Cl₂ (395.73 mg, 540.83 μmol, 0.1eq) in dioxane (40 mL) andH₂O (8 mL) was de -gassed and then heated to 80° C. overnight underN_(2.) TLC (PE:EtOAc=1:1) showed the starting material was consumedcompletely. The reaction mixture was poured into H₂O (300 mL). Themixture was extracted with EtOAc (3×250 mL). The organic phase waswashed with saturated brine (300 mL), dried over anhydrous MgSO₄,concentrated in vacuum to give a residue, which was purified by silicagel column chromatography (PE/EtOAc=5/1) to affordN¹-(3-(4-amino-3-nitropyridin-2-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(CIX) (1.50 g, 4.70 mmol, 86.9% yield) as a solid. ESIMS found forC₁₅H₁₈FN₅O₂ m/z 320.1(M+H).

Step 4

To a solution ofN¹-(3-(4-amino-3-nitropyridin-2-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine(CIX) (1.50 g, 4.70 mmol, 1.0 eq) in MeOH (30 mL) was added Zn (1.54 g,23.50 mmol, 5.0 eq) and NH₄Cl (754.21mg, 14.10 mmol, 3.0 eq) in oneportion at room temperature. The mixture was stirred at room temperaturefor 10 min. TLC showed the reaction was completed. The mixture wasfiltered and concentrated in vacuum to afford5-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)pyridine-3,4-diamine(CX) (1.2 g, 4.15 mmol, 4.15 mmol, 88.2% yield) as a yellow oil. ¹H NMR(CD₃OD, 300 MHz) 2.44 (s, 6H), 2.78 (t, J=5.25 Hz, 2H), 3.24-3.34 (m,2H), 6.40-6.51(m, 2H), 6.53 (d, J=1.5 Hz, 1H), 6.71(d, J=6.3 Hz, 1H),7.58 (d, J=6.6 Hz, 1H); ESIMS found for C₁₅H₂₀FN₅ m/z 290.1(M+H).

Example 1

Preparation of3-(4-(5-Methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine(353) is depicted below in Scheme 21.

Step 1

A solution of5-bromo-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl1-carbaldehyde(XIX) (872 mg, 2.81mmol, 1.0 eq), bis(pinacolato)diboron (898 mg, 3.37mmol,), and KOAc (824 mg, 8.4 mmol, 3.0 eq) in dry DMF (40 mL) waspurged with argon. PdCl₂(dppf)₂ (120 mg, 0.14 mmol, 0.05) was added tothe solution and purged again with argon. The solution was heated at 90°C. for 2 h under argon and cooled to the room temperature. The reactionmixture was diluted in water (30 mL) and extracted with DCM (30×3). Thecombined organic layers were dried over Na₂SO_(4,) filtered andconcentrated in vacuo to give1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde(CXI) which was used for the next step without further purification.

Step 2

A solution of1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde(CXI) (1.0 g, 2.80 mmol, 1.0 eq),3-bromo-5-(piperidin-1-ylmethyl)pyridine (XLIII) (717 mg, 2.80 mmol, 1.0eq), Pd(dppf)Cl₂ (144 mg, 0.196 mmol, 0.07 eq) and Na₂CO₃ (0.89 g, 8.40mmol, 3.0 eq) in a mixed solvent of 1,2-dimethoxyethane (30mL) and H₂O(5 mL) was refluxed for 3 h under a nitrogen atmosphere. The reactionmixture was diluted in water (30 mL) and extracted with DCM (30×3). Thecombined organic layers were dried over Na₂SO_(4,) filtered andconcentrated in vacuo, the resultant residue was purified by flashchromatography on silica gel eluting with 100% EtOAc to give the5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde(CXII) (1.04 g, 2.56 mmol, 91.3% for 2 steps) as a yellow solid. ¹H NMR(CDCl₃, 400 MHz) δppm 1.27 (t, J=7.6 Hz, 2H), 1.40-1.52 (m, 4H),1.66-1.77 (m, 1H), 1.79-1.95 (m, 2H), 2.02-2.14 (m, 1H), 23.17-2.30 (m,1H), 2.35-2.53 (m, 4H), 2.62-2.76 (m, 1H), 3.58 (s, 2H), 3.89 (dd, J=9.2Hz, J=11.2 Hz, 1H), 4.08-4.24 (m, 1H), 6.30 (dd, J=2 Hz, J=10.4 Hz, 1H),7.95 (s, 1H), 8.60 (s, 1H), 8.78 (s, 1H), 8.88 (s, 1H), 10.27 (s, 1H);ESIMS found C₂₃H₂₇N₅₀₂ m/z 406.1(M+H).

Step 3

A solution of5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde(CXII) (100.0 mg, 0.25 mmol, 1.0 eq),2-(5-methylthiophen-2-yl)pyridine-3,4-diamine (LXXIX) (50.6 mg, 0.25mmol, 1.0 eq) and Na₂S₂O₅ (56.3 mg, 0.30 mmol, 1.2 eq) in DMF (2 mL) wasstirred at 120° C. for 24 h. LC/MS showed the starting material wasconsumed. Water (5 mL) was added in dropwise and the mixture wasfiltered. The filtrate was washed by MeOH (0.5 mL) and used for directlyfor next step without further purification.

Step 4

Crude3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine(CXIII) was mixed with in HCl/EtOAc (15 mL) was stirred at 10-35° C. for12 h. LC/MS showed the starting material was consumed. The mixture wasconcentrated to give a residue. The residue was purified by pre-HPLC(HCl) to give3-(4-(5-Methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine(353) (11.0 mg, 0.02 mmol, 8.8% yield for 2 steps) as a white solid. ¹HNMR (DMSO-d₆, 400 MHz) δppm 1.33-1.49 (m, 1H), 1.68-1.77 (m, 1H),1.78-1.96 (m, 4H), 2.57 (s, 3H), 2.92-3.05 (m, 2H), 3.42 (d, J=10.42 Hz,2H), 4.45-4.53 (m, 2H), 7.06 (d, J=3.39 Hz, 1H), 7.65 (d, J=6.40 Hz,1H), 8.28 (d, J=6.40 Hz, 1H), 8.54 (d, J=3.76 Hz, 1H), 8.83 (d, J=5.90Hz, 2H), 9.03 (s, 1H), 9.11(s, 2H), 11.26 (brs, 1H), 14.75 (brs, 2H);ESIMS found for C₂₈H₂₆N₈5 m/z 507.1(M+1).

The following compound was prepared in accordance with the proceduredescribed in the above Example 1.

N-(5-(3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]1pyridin-5-yl)pyridin-3-yl)propionamide1.

White solid (31.0 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.15(t, J=7.53 Hz, 3H), 2.45 (q, J=7.61Hz, 2H), 7.28 (td, J=8.40 Hz, J=2.28Hz, 1H), 7.57 (d, J=5.52 Hz, 1H), 7.66 (q, J=6.4 Hz, 1H), 8.47 (d,J=5.27 Hz, 1H), 8.61(s, 1H), 8.77 (dd, J=7.78, 1.76 Hz, 3H), 8.82 (d,J=7.65 Hz, 1H), 9.04 (d, J=1.88 Hz, 1H), 9.11(d, J=1.51Hz, 1H), 10.31(s,1H), 13.87 (brs, 1H); ESIMS found for C₂₆H₁₉FN₈O m/z 479.1(M+1).

5-(3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N,N-dimethylpyridin-3-amine7.

White solid (38.6 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 3.06(s, 6H), 7.32 (td, J=8.28 Hz, J=2.28 Hz, 1H), 7.45 (brs, 1H), 7.53-7.62(m, 2H), 8.22 (d, J=2.26 Hz, 1H), 8.33 (s, 1H), 8.47 (d, J=5.40 Hz, 1H),8.73 (d, J=7.78 Hz, 1H), 8.83 (d, J=10.79 Hz, 1H), 9.06 (s, 1H), 9.09(s, 1H), 13.83 (s, 1H), 14.54 (s, 1H); ESIMS found for C₂₅H₁₉FN₈ m/z451.1(M+1).

1-(5-(3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine13.

White solid (3.2 mg, 0.007 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm2.81(brs, 6H), 4.43-4.50 (m, 2H), 7.48-7.56 (m, 1H), 7.69-7.79 (m, 1H),7.87 (brs, 1H), 8.52-8.61(m, 3H), 8.69 (brs, 1H), 8.83 (d, J=1.51Hz,1H), 9.13 (s, 1H), 9.15 (d, J=2.01Hz, 1H), 9.17 (d, J=1.63 Hz, 1H),10.74 (brs, 1H), 14.64 (s, 1H), 14.84 (brs, 1H); ESIMS found forC₂₆H₂₁FN8 m/z 465.1(M+1).

N-(5-(3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide19.

White solid (20.0 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm0.86-0.97 (m, 4H), 1.91-1.98 (m, 1H), 7.53 (qd, J=8.16 Hz, J=2.0 Hz,1H), 7.82 (q, J=6.28 Hz, 1H), 7.98 (d, J=6.27 Hz, 1H), 8.50 (d, J=11.04Hz, 1H), 8.54-8.62 (m, 2H), 8.80 (s, 1H), 8.90 (s, 1H), 8.95 (s, 1H),8.99 (d, J=1.88 Hz, 1H), 9.07 (d, J=2.01Hz, 1H), 11.22 (brs, 1H), 14.98(brs, 1H), 14.94 (brs, 1H); ESIMS found for C₂₇H₁₉FN₈O m/z 491.2 (M+1).

5-(5-((3,3-Difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-imidazo[5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine25.

White solid (12.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm2.60-2.73 (m, 2H), 3.86-3.98 (m, 4H), 4.65 (brs, 2H), 7.58 (td, J=8.34,1.88 Hz, 1H), 7.78-7.87 (m, 1H), 8.01(d, J=6.27 Hz, 1H), 8.52-8.70 (m,3H), 8.81(s, 1H), 8.95 (d, J=1.25 Hz, 1H), 9.08 (d, J=2.01Hz, 1H), 9.18(d, J=2.26 Hz, 1H), 9.20 (d, J=1.76 Hz, 1H), 14.97 (brs, 1H), 15.07(brs, 1H); ESIMS found for C₂₈H_(2,)F₃N₈ m/z 527.2 (M+1).

N-(5-(3-(4-(4-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide28.

White solid (25.0 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.00(d, J=6.65 Hz, 6H), 2.15-2.26 (m, 1H), 2.35 (d, J=7.15 Hz, 2H), 7.68 (t,J=8.72 Hz, 2H), 7.97 (d, J=5.27 Hz, 1H), 8.58 (d, J=6.40 Hz, 1H),8.68-8.76 (m, 2H), 8.83 (s, 2H), 8.87 (s, 1H), 8.99 (d, J=2.01Hz, 1H),9.12 (d, J=2.13 Hz, 1H), 10.67 (brs, 1H), 14.92 (s, 1H), 14.94 (brs,1H); ESIMS found for C₂₈H₂₃FN₈O m/z 507.1(M+1).

N-(5-(3-(4-(4-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide34.

White solid (50.0 mg, 0.10 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.33(s, 9H), 7.66 (t, J=8.78 Hz, 2H), 7.96 (d, J=6.27 Hz, 1H), 8.57 (d,J=6.40 Hz, 1H), 8.68-8.76 (m, 2H), 8.86-8.93 (m, 2H), 9.00 (d, J=2.01Hz,1H), 9.02 (d, J=1.76 Hz, 1H), 9.11(d, J=2.01Hz, 1H), 9.97 (s, 1H), 14.92(s, 2H); ESIMS found for C₂₈H₂₃FN₈O m/z 507.2 (M+1).

3-(4-(4-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine40.

White solid (9.0 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 2.00 (brs,4H), 3.04 (brs, 4H), 4.20 (s, 2H), 7.30 (t, J=8.60 Hz, 2H), 7.56 (d,J=5.40 Hz, 1H), 8.33 (s, 1H), 8.38 (d, J=5.52 Hz, 1H), 8.43-8.50 (m,2H), 8.56-8.66 (m, 2H), 8.71(s, 1H), 8.97 (d, J=1.51Hz, 1H), 9.01(d,J=1.51Hz, 1H), 9.17 (d, J=1.76 Hz, 1H); ESIMS found for C281⁻123FN8m/z491.2 (M+1).

N-(5-(3-(4-(4-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide46.

White solid (8.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm1.81-1.94 (m, 1H), 1.94-2.06 (m, 1H), 2.14-2.26 (m, 2H), 2.28-2.39 (m,3H), 7.70 (t, J=8.85 Hz, 2H), 7.96 (d, J=4.64 Hz, 1H), 8.58 (d, J=6.27Hz, 1H), 8.69-8.76 (m, 2H), 8.78 (s, 1H), 8.82-8.89 (m, 2H), 9.00 (d,J=2.13 Hz, 1H), 9.12 (d, J=2.26 Hz, 1H), 10.48 (s, 1H), 14.91(brs, 2H);ESIMS found for C₂₈H₂₁FN₈O m/z 505.1(M+1).

3-(4-(4-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine52.

White solid (78.1mg, 0.19 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 7.62 (t,J=8.60 Hz, 2H), 8.01(d, J=6.15 Hz, 1H), 8.59 (d, J=6.40 Hz, 1H), 8.68(brs, 2H), 9.10 (d, J=2.13 Hz, 1H), 9.17 (d, J=2.38 Hz, 1H), 9.31(s,1H), 9.34 (s, 2H), 14.95 (s, 1H), 15.03 (brs, 1H); ESIMS found forC₂₂H₁₃FN₈ m/z 409.0 (M+1).

5-(3-(4-(2-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine55.

White solid (11.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 6.75(s, 1H), 7.58-7.68 (m, 2H), 7.76-7.86 (m, 1H), 7.95 (brs, 1H), 8.12 (d,J=2.13 Hz, 2H), 8.18 (brs, 1H), 8.47 (s, 1H), 8.68 (d, J=6.40 Hz, 1H),8.91(brs, 1H), 9.03 (d, J=2.13 Hz, 1H), 15.02 (s, 1H), 15.06 (brs, 1H);ESIMS found for C₂₃H₁₅FN₈ m/z 423.1(M+1).

N-(5-(3-(4-(2-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide61.

White solid (12.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 300 MHz) δppm 1.20(d, J=6.78 Hz, 6H), 2.65-2.77 (m, 1H), 7.52-7.64 (m, 2H), 7.67-7.80 (m,1H), 8.04 (d, J=5.27 Hz, 1H), 8.16 (brs, 1H), 8.61(brs, 1H), 8.66 (d,J=6.41Hz, 1H), 8.69 (brs, 1H), 8.77 (d, J=1.88 Hz, 1H), 8.86 (brs, 1H),9.04 (d, J=1.88 Hz, 1H), 10.35 (s, 1H), 14.85 (s, 1H); ESIMS found forC₂₇H₂₁FN₈O m/z 493.2 (M+1).

N-(5-(3-(4-(2-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide68.

White solid (13.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.08(s, 9H), 2.34 (s, 2H), 7.56-7.64 (m, 2H), 7.72-7.81(m, 1H), 8.07-8.14(m, 1H), 8.19 (brs, 1H), 8.66 (brs, 1H), 8.68 (d, J=6.40 Hz, 1H), 8.77(brs, 1H), 8.84-8.94 (m, 2H), 9.04 (d, J=2.26 Hz, 1H), 10.64 (brs, 1H),14.90-15.25 (m, 1H), 14.96 (brs, 1H); ESIMS found for C₂₉H₂₅FN₈O m/z521.2 (M+1).

N-(5-(3-(4-(2-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide73.

White solid (10.0 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 1.68-1.77(m, 2H), 1.77-1.88 (m, 2H), 1.89-1.99 (m, 2H), 2.00-2.10 (m, 2H), 2.98(quin, J=8.03 Hz, 1H), 7.54 (dd, J=10.48, 8.72 Hz, 1H), 7.63 (t, J=7.64Hz, 1H), 7.79 (q, J=8.12 Hz, 1H), 8.17 (d, J=6.40 Hz, 1H), 8.30 (brs,1H), 8.62 (d, J=6.53 Hz, 1H), 8.94 (s, 2H), 9.04 (s, 1H), 9.12 (s, 1H),9.28 (brs, 1H); ESIMS found for C₂₉H₂₃FN₈O m/z 519.2 (M+1).

5-(Pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine82.

White solid (11.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 7.89(d, J=5.40 Hz, 1H), 8.01-8.14 (m, 2H), 8.62 (d, J=5.90 Hz, 1H), 8.86 (d,J=7.91Hz, 1H), 8.90 (d, J=5.27 Hz, 1H), 8.98 (d, J=4.52 Hz, 1H), 9.16(d, J=2.13 Hz, 1H), 9.19 (d, J=1.88 Hz, 1H), 9.39 (s, 1H), 9.49 (brs,1H), 10.06 (brs, 1H), 14.58 (s, 1H), 14.90 (brs, 1H); ESIMS found forC₂₂H₁₄N₈ m/z 391.1(M+1).

N-(5-(3-(4-(Pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide87.

White solid (12.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 300 MHz) δppm 1.19(d, J=6.78 Hz, 6H), 2.65-2.79 (m, 1H), 7.79 (d, J=6.03 Hz, 1H), 7.96(brs, 1H), 8.59 (d, J=6.03 Hz, 1H), 8.67 (s, 1H), 8.82 (brs, 3H),9.00-9.11(m, 2H), 9.41(brs, 1H), 9.88 (brs, 1H), 10.37 (s, 1H), 14.37(brs, 1H), 14.76 (s, 1H); ESIMS found for C₂₆H₂,N₉O m/z 476.3 (M+1).

N-Isopropyl-5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine90.

White solid (12.5 mg, 0.03 mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 1.34 (d,J=6.40 Hz, 7H), 3.86 (spt, J=6.40 Hz, 1H), 8.03 (s, 1H), 8.09 (d, J=2.26Hz, 1H), 8.13-8.20 (m, 2H), 8.43 (s, 1H), 8.70 (d, J=6.27 Hz, 1H), 9.02(d, J=2.01Hz, 1H), 9.05 (d, J=5.14 Hz, 1H), 9.17 (d, J=2.13 Hz, 1H),9.27 (d, J=8.16 Hz, 1H), 10.01(d, J=1.25 Hz, 1H); ESIMS found forC₂₅H_(2,)N₉ m/z 448.1(M+1).

5-(5-(Piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine93.

White solid (13.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm1.36-1.47 (m, 1H), 1.68-1.76 (m, 1H), 1.78-1.90 (m, 4H), 2.93-3.04 (m,2H), 3.45 (d, J=11.80 Hz, 2H), 4.57 (brs, 2H), 7.90 (d, J=5.77 Hz, 1H),8.14 (dd, J=7.72, 5.71Hz, 1H), 8.63 (d, J=5.90 Hz, 1H), 8.97 (s, 1H),8.99-9.05 (m, 2H), 9.20 (s, 2H), 9.32 (d, J=1.76 Hz, 1H), 9.45-9.52 (m,1H), 10.13 (brs, 1H), 11.24 (brs, 1H), 14.64 (s, 1H), 14.91(brs, 1H);ESIMS found for C₂₈H₂₅N₉ M/Z 488.2 (M+1).

N-Benzyl-1-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine101.

White solid (9.3 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm4.31(brs, 2H), 4.47 (brs, 2H), 7.40-7.49 (m, 3H), 7.61-7.67 (m, 2H),7.88 (d, J=5.65 Hz, 1H), 8.07 (brs, 1H), 8.62 (d, J=5.90 Hz, 1H),8.84-8.90 (m, 2H), 8.93 (d, J=5.15 Hz, 1H), 9.18 (s, 2H), 9.23 (s, 1H),9.46 (brs, 1H), 10.08 (brs, 3H), 14.57 (brs, 1H), 14.88 (brs, 1H); ESIMSfound for C₃₀H₂₃N₉ m/z 510.1(M+1).

5-(4-Methylpyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine109.

White solid (55.3 mg, 0.14 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 2.63(s, 3H), 7.84 (d, J=5.52 Hz, 1H), 8.05 (d, J=5.65 Hz, 1H), 8.64 (d,J=5.40 Hz, 1H), 8.83-8.91(m, 2H), 9.01(d, J=6.15 Hz, 2H), 9.05 (d,J=2.51Hz, 2H), 9.30 (d, J=4.64 Hz, 2H), 14.34 (brs, 1H), 14.90 (brs,1H); ESIMS found for C₂₃H₁₆N₈ m/z 405.0 (M+1).

2-Phenyl-N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide114.

White solid (14.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 3.85(s, 2H), 7.21-7.28 (m, 1H), 7.33 (t, J=7.53 Hz, 2H), 7.42 (d, J=7.15 Hz,2H), 7.83 (d, J=5.27 Hz, 1H), 8.66 (d, J=5.40 Hz, 1H), 8.83 (s, 1H),8.86 (s, 1H), 8.93 (s, 1H), 9.07-9.16 (m, 4H), 9.35 (d, J=3.76 Hz, 2H),11.02 (brs, 1H), 14.30 (brs, 1H), 14.81(s, 1H); ESIMS found forC₃₀H₂,N₉O m/z 524.1(M+1).

N-(5-(3-(4-(Pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide121.

White solid (39.0 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 0.98(t, J=7.34 Hz, 3H), 1.71(sxt, J=7.43 Hz, 2H), 7.83 (d, J=5.40 Hz, 1H),8.65 (d, J=5.40 Hz, 1H), 8.97 (s, 2H), 9.01(s, 1H), 9.08-9.16 (m, 4H),9.34-9.43 (m, 2H), 10.98 (brs, 1H), 14.32 (brs, 1H), 14.83 (s, 1H);ESIMS found for C₂₆H₂₁N₉O m/z 476.2 (M+1).

N-(5-(3-(4-(Pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide126.

White solid (8.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm1.19-1.39 (m, 4H), 1.41-1.54 (m, 2H), 1.62-1.72 (m, 1H), 1.79 (d,J=10.16 Hz, 2H), 1.93 (d, J=11.29 Hz, 2H), 7.84 (d, J=4.77 Hz, 1H), 8.65(d, J=5.15 Hz, 1H), 8.97 (brs, 1H), 9.03 (brs, 2H), 9.07-9.17 (m, 4H),9.37 (brs, 2H), 10.94 (brs, 1H), 14.35 (brs, 1H), 14.85 (brs, 1H); ESIMSfound for C29H25N90 m/z 516.3 (M+1).

N-((5-(3-(4-(Pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine136.

White solid (11.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.30(t, J=7.22 Hz, 3H), 3.01-3.13 (m, 2H), 4.36 (t, J=5.27 Hz, 2H), 7.83(dd, J=7.34, 5.08 Hz, 1H), 8.10 (d, J=6.27 Hz, 1H), 8.36-8.45 (m, 1H),8.62 (d, J=6.40 Hz, 1H), 8.83 (d, J=1.25 Hz, 1H), 8.87 (s, 1H), 9.01(d,J=4.27 Hz, 1H), 9.18-9.28 (m, 3H), 9.60-9.73 (m, 3H), 15.07 (s, 1H),15.22 (s, 1H); ESIMS found for C₂₅H₂₁N₉m/z 448.3 (M+1).

N-(5-(3-(4-(Pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide141.

White solid (12.0 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 7.59-7.67(m, 3H), 7.72 (t, J=7.4 Hz, 1H), 8.12 (dd, J=10.35, 6.96 Hz, 3H),8.41(t, J=7.53 Hz, 1H), 8.61(d, J=6.40 Hz, 1H), 8.96 (d, J=4.27 Hz, 1H),9.16 (d, J=2.01Hz, 1H), 9.19 (s, 1H), 9.38 (d, J=1.51Hz, 1H), 9.42 (d,J=1.88 Hz, 1H), 9.49 (s, 1H), 9.77 (d, J=7.78 Hz, 1H); ESIMS found forC₂₉H₁₉N₉O m/z 510.2 (M+1).

N-(5-(3-(4-(Pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide148.

White solid (38.0 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 300 MHz) δppm 0.93(t, J=7.16 Hz, 3H), 1.38 (sxt, J=7.53 Hz, 2H), 1.65 (quin, J=7.53 Hz,2H), 7.73 (brs, 1H), 8.12 (d, J=4.14 Hz, 1H), 8.47 (d, J=6.03 Hz, 1H),8.62 (d, J=5.27 Hz, 1H), 8.88 (brs, 1H), 8.94 (brs, 2H), 8.97 (brs, 1H),9.05 (s, 1H), 9.10 (brs, 1H), 9.50-9.59 (m, 1H), 11.23 (brs, 1H), 15.15(brs, 1H), 15.34 (brs, 1H); ESIMS found for C₂₇H₂₃N₉O m/z 490.3 (M+1).

N-(5-(3-(4-(Piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide157.

White solid (49.4 mg, 0.11mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.14 (t,J=7.53 Hz, 3H), 1.70 (brs, 6H), 2.42 (q, J=7.49 Hz, 2H), 4.22 (brs, 4H),6.90 (brs, 1H), 7.78 (d, J=5.90 Hz, 1H), 8.66 (s, 2H), 8.71(s, 1H), 8.93(d, J=1.88 Hz, 1H), 9.03 (d, J=2.01Hz, 1H), 10.31(s, 1H), 13.61(brs,1H), 14.40 (brs, 1H); ESIMS found for C₂₅H₂₅N₉O m/z 468.2 (M+1).

N,N-Dimethyl-5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine163.

White solid (41.0 mg, 0.09 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.78(brs, 6H), 3.16 (s, 6H), 4.34 (brs, 4H), 7.14 (d, J=6.78 Hz, 1H), 7.74(d, J=6.65 Hz, 1H), 8.06 (brs, 1H), 8.26 (brs, 1H), 8.54 (brs, 1H), 8.97(d, J=2.01Hz, 1H), 9.15 (d, J=2.01Hz, 1H), 13.30 (brs, 1H), 14.56 (s,1H), 14.74 (s, 1H); ESIMS found for C2-(H25N9 M/Z 440.1(M+1).

N,N-Dimethyl-1-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine169.

White solid (10.6 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.69(brs, 6H), 2.25 (s, 6H), 3.58 (brs, 2H), 4.17 (brs, 4H), 6.82 (d, J=5.40Hz, 1H), 7.81(d, J=5.52 Hz, 1H), 8.10 (s, 1H), 8.15 (brs, 2H), 8.56 (d,J=1.51Hz, 1H), 8.95 (d, J=2.01Hz, 1H), 8.98 (d, J=2.13 Hz, 1H), 9.06 (d,J=2.13 Hz, 1H), 13.35 (s, 1H), 14.32 (brs, 1H); ESIMS found for C₂₅H₂₇N₉m/z 454.2 (M+1).

N-(5-(3-(4-(Piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide175.

White solid (17.0 mg, 0.04 mmol). ¹1-1NMR (DMSO-d₆, 400 MHz) 6 ppm0.83-0.93 (m, 4H), 1.78 (d, J=7.40 Hz, 6H), 1.86-1.96 (m, 1H), 4.31(brs,4H), 7.11(d, J=6.78 Hz, 1H), 7.71(d, J=6.65 Hz, 1H), 8.67 (s, 1H), 8.75(s, 2H), 8.83 (s, 1H), 9.07 (d, J=1.63 Hz, 1H), 10.86 (brs, 1H), 12.95(brs, 1H), 14.44 (s, 1H), 14.62 (s, 1H); ESIMS found for C₂₆H₂₅N₉O m/z480.3 (M+1).

5-(5-((3,3-Difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine181.

White solid (8.0 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 1.82 (brs,6H), 2.26-2.40 (m, 2H), 2.85 (t, J=6.84 Hz, 2H), 2.98 (t, J=13.11Hz,2H), 3.80 (s, 2H), 4.19 (brs, 4H), 6.97 (d, J=5.40 Hz, 1H), 7.60 (d,J=4.77 Hz, 1H), 8.09 (brs, 1H), 8.44 (d, J=1.76 Hz, 1H), 8.57 (s, 1H),8.74 (brs, 2H), 8.83 (brs, 1H); ESIMS found for C₂₇H₂₇F₂N₉ m/z 516.3(M+1).

3-Methyl-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide184.

White solid (13.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 0.97(d, J=6.65 Hz, 6H), 2.05-2.19 (m, 1H), 2.23 (s, 3H), 2.28 (d, J=7.03 Hz,2H), 7.49 (d, J=5.65 Hz, 1H), 8.20 (d, J=5.40 Hz, 1H), 8.27 (s, 1H),8.49 (s, 1H), 8.73 (s, 1H), 8.85 (d, J=1.51Hz, 1H), 8.99 (d, J=3.14 Hz,2H), 9.01(s, 1H), 10.31(s, 1H); ESIMS found for C₂₆H₂₄N₁₀0 m/z 493.2(M+1).

N-(5-(3-(4-(4-Methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide190.

White solid (7.8 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.25 (s,9H), 2.53 (s, 3H), 6.79 (d, J=5.65 Hz, 1H), 6.99 (brs, 2H), 8.04 (d,J=5.77 Hz, 1H), 8.39 (t, J=2.20 Hz, 1H), 8.73 (d, J=2.01Hz, 1H), 8.76(d, J=2.13 Hz, 1H), 8.91(d, J=2.26 Hz, 1H), 8.93 (d, J=2.13 Hz, 1H),8.96 (s, 1H), 9.55 (s, 1H); ESIMS found for C₂₆H₂₄N₁₀0 m/z 493.2 (M+1).

3-(4-(4-Methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine196.

White solid (14.4 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm1.87-2.00 (m, 2H), 2.00-2.12 (m, 2H), 2.48 (s, 3H), 3.10-3.24 (m, 3H),3.38-3.50 (m, 6H), 4.63 (brs, 2H), 7.72-7.77 (m, 1H), 8.33-8.38 (m, 1H),8.66 (s, 1H), 8.90-9.00 (m, 2H), 9.20 (d, J=2.01Hz, 1H), 9.27-9.35 (m,2H), 10.37 (d, J=1.38 Hz, 1H), 11.74 (brs, 1H), 14.39 (brs, 1H), 14.82(brs, 1H); ESIMS found for C₂₆H₂₄N₁₀ m/z 477.1(M+1).

5-(3-(4-(4-Methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine211.

White solid (11.9 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 2.88(s, 3H), 3.73 (d, J=12.30 Hz, 2H), 3.87 (brs, 2H), 5.32-5.47 (m, 2H),6.74 (brs, 1H), 7.24 (d, J=5.52 Hz, 1H), 7.89 (d, J=6.53 Hz, 1H),8.01(s, 1H), 8.10 (d, J=2.01Hz, 1H), 8.54 (s, 1H), 8.95 (d, J=1.63 Hz,1H), 9.03 (d, J=2.01Hz, 1H), 11.33 (brs, 1H), 14.48 (brs, 1H), 14.74(brs, 1H); ESIMS found for C₂₂H₂₂N₁₀ m/z 427.1(M+1).

N-(5-(3-(4-(4-Methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide217.

White solid (17.3 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.17(d, J=6.78 Hz, 6H), 2.24 (s, 3H), 2.53 (brs, 4H), 2.68 (spt, J=6.87 Hz,1H), 4.20 (brs, 4H), 6.87 (d, J=5.52 Hz, 1H), 7.84 (d, J=5.52 Hz, 1H),8.17 (s, 1H), 8.65 (d, J=2.01Hz, 1H), 8.72 (d, J=1.76 Hz, 2H), 8.91(d,J=2.26 Hz, 1H), 9.01(d, J=2.26 Hz, 1H), 10.28 (s, 1H), 13.38 (brs, 1H),14.37 (brs, 1H); ESIMS found for C₂₆H₂₈N₁₀O m/z 497.2 (M+1).

3-(4-(4-Methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine223.

White solid (11.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm1.33-1.49 (m, 1H), 1.67-1.76 (m, 1H), 1.77-1.94 (m, 4H), 2.87 (d, J=4.14Hz, 3H), 2.95-3.07 (m, 2H), 3.37-3.55 (m, 6H), 4.02 (t, J=12.99 Hz, 2H),4.55 (d, J=4.77 Hz, 2H), 5.43 (d, J=13.80 Hz, 2H), 7.26 (d, J=6.78 Hz,1H), 7.84 (d, J=6.78 Hz, 1H), 8.98 (s, 1H), 9.00 (d, J=2.01Hz, 1H), 9.07(brs, 1H), 9.19 (d, J=2.13 Hz, 1H), 9.33 (d, J=1.76 Hz, 1H), 11.48 (brs,1H), 11.72 (brs, 1H), 14.62 (brs, 1H), 14.77 (brs, 1H); ESIMS found forC₂₈H₃₂N₁₀ m/z 509.2 (M+1).

N-(5-(3-(4-(4-Methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide229.

White solid (12.0 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 1.67-1.76(m, 2H), 1.77-1.86 (m, 2H), 1.87-1.99 (m, 2H), 2.01-2.11(m, 2H),2.99-3.10 (m, 1H), 3.06 (s, 3H), 3.52-3.65 (m, 2H), 3.89-3.99 (m, 2H),4.01-4.13 (m, 2H), 5.41-5.53 (m, 2H), 7.40 (d, J=6.78 Hz, 1H), 7.87 (d,J=6.90 Hz, 1H), 9.03 (d, J=1.88 Hz, 1H), 9.08 (s, 2H), 9.11(d, J=1.88Hz, 1H), 9.39 (s, 1H); ESIMS found for C₂₈H₃₀N₁₀O m/z 523.3 (M+1).

3-(4-(4-Methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine234.

White solid (4.8 mg, 0.01mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 3.07 (s,3H), 3.51-3.68 (m, 2H), 3.78-3.91(m, 2H), 3.93-4.09 (m, 1H), 5.36-5.55(m, 1H), 7.42 (d, J=6.90 Hz, 1H), 7.87 (d, J=6.78 Hz, 1H), 9.03-9.09 (m,2H), 9.25-9.31(m, 3H); ESIMS found for C₂₁H₂₀N₁₀ m/z 413.1(M+1).

5-(4-Methylpyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine239.

White solid (26.0 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 2.60(s, 3H), 7.89-7.95 (m, 2H), 8.02 (d, J=5.77 Hz, 1H), 8.48 (d, J=6.53 Hz,1H), 8.55 (d, J=5.02 Hz, 1H), 8.84 (d, J=5.77 Hz, 1H), 8.88 (d,J=2.01Hz, 1H), 9.01(s, 1H), 9.05 (d, J=2.26 Hz, 1H), 9.43 (d, J=1.26 Hz,1H), 14.98 (brs, 1H), 15.02 (s, 1H); ESIMS found for C₂₂H₁₅N₇S m/z 410.0(M+1).

N-(5-(3-(4-(Thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide245.

White solid (33.0 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm7.56-7.63 (m, 2H), 7.67 (t, J=7.28 Hz, 1H), 7.87 (d, J=6.40 Hz, 1H),7.90 (dd, J=5.08, 2.95 Hz, 1H), 8.13 (d, J=7.28 Hz, 2H), 8.44 (d, J=6.53Hz, 1H), 8.52 (d, J=5.02 Hz, 1H), 9.03 (s, 1H), 9.08 (d, J=1.88 Hz, 1H),9.09-9.14 (m, 2H), 9.19 (d, J=1.63 Hz, 1H), 9.40 (d, J=1.38 Hz, 1H),11.10 (s, 1H), 14.93 (brs, 2H); ESIMS found for C₂₈H₁₈N₈OS m/z515.1(M+1).

N-(5-(3-(4-(Thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide251.

White solid (14.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 0.97(t, J=7.40 Hz, 3H), 1.70 (sxt, J=7.28 Hz, 2H), 2.46 (t, J=7.16 Hz, 3H),7.90 (d, J=6.40 Hz, 1H), 7.98 (dd, J=5.08, 2.95 Hz, 1H), 8.48 (d, J=6.27Hz, 1H), 8.52 (d, J=4.27 Hz, 1H), 8.87 (brs, 1H), 8.92 (d, J=1.25 Hz,1H), 8.95 (brs, 1H), 9.07 (s, 1H), 9.10 (d, J=2.01Hz, 1H), 9.36 (brs,1H), 10.81(brs, 1H), 14.88-15.04 (m, 2H); ESIMS found for C₂₅H₂₀N₈OS m/z481.2 (M+1).

N-Benzyl-1-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine257.

White solid (32.1mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm4.31(brs, 2H), 4.47 (brs, 2H), 7.40-7.49 (m, 3H), 7.61-7.67 (m, 2H),7.88 (d, J=5.65 Hz, 1H), 8.07 (brs, 1H), 8.62 (d, J=5.90 Hz, 1H),8.84-8.90 (m, 2H), 8.93 (d, J=5.15 Hz, 1H), 9.18 (s, 2H), 9.23 (s, 1H),9.46 (brs, 1H), 10.08 (brs, 3H), 14.57 (s, 1H), 14.88 (brs, 1H); ESIMSfound for C₂₉H₂₂N₈S m/z 515.2 (M+1).

N-((5-(3-(4-(Furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine266.

White solid (12.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.30(t, J=7.28 Hz, 3H), 3.02-3.14 (m, 2H), 4.35 (t, J=5.83 Hz, 2H), 7.84 (s,1H), 7.91(d, J=6.65 Hz, 1H), 8.12 (t, J=1.76 Hz, 1H), 8.50 (d, J=6.53Hz, 1H), 8.72 (s, 1H), 8.84 (d, J=1.76 Hz, 1H), 9.17 (d, J=2.13 Hz, 1H),9.20 (d, J=2.01Hz, 1H), 9.24 (d, J=2.01Hz, 1H), 9.43 (brs, 2H), 9.47 (s,1H), 14.97 (s, 2H); ESIMS found for C₂₄H₂₀N₈O m/z 437.2 (M+1).

5-(3-(4-(Furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N-isopropylpyridin-3-amine272.

White solid (10.0 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 1.36 (d,J=6.53 Hz, 6H), 3.87-3.95 (m, 1H), 7.50 (dd, J=2.01, 0.75 Hz, 1H),7.95-7.99 (m, 2H), 8.01-8.05 (m, 1H), 8.09 (d, J=2.51Hz, 1H), 8.43 (d,J=0.75 Hz, 1H), 8.45 (d, J=6.52 Hz, 1H), 9.02 (d, J=2.01Hz, 1H), 9.24(d, J=2.26 Hz, 1H), 9.37 (s, 1H); ESIMS found for C₂₄H₂₀N₈O m/z437.1(M+1).

N-(5-(3-(4-(Furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide278.

White solid (20.0 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 0.92(t, J=7.40 Hz, 3H), 1.37 (sxt, J=7.52 Hz, 2H), 1.64 (quin, J=7.52 Hz,2H), 2.42 (t, J=7.40 Hz, 2H), 7.55 (brs, 2H), 7.91(brs, 1H), 8.39 (d,J=5.52 Hz, 1H), 8.61(s, 1H), 8.78 (dd, J=7.28, 2.01Hz, 2H), 8.98-9.05(m, 1H), 9.02 (d, J=2.26 Hz, 1H), 9.07 (d, J=2.01Hz, 1H), 10.40 (s, 1H),14.05 (brs, 1H), 14.67 (brs, 1H); ESIMS found for C₂₆H₂₂N₈O₂ m/z 479.2(M+1).

1-Cyclopentyl-N-((5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine284.

White solid (11.7 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm1.16-1.38 (m, 2H), 1.44-1.67 (m, 4H), 1.81(d, J=2.38 Hz, 2H), 2.22-2.36(m, 1H), 2.97 (brs, 2H), 4.34 (brs, 2H), 7.86 (d, J=6.78 Hz, 2H),8.00-8.14 (m, 1H), 8.38-8.51(m, 1H), 8.71(brs, 1H), 8.84 (brs, 1H),9.05-9.23 (m, 3H), 9.34-9.58 (m, 3H), 14.92 (brs, 2H); ESIMS found forC₂₈H₂₆N₈O m/z 491.2 (M+1).

N-(5-(3-(4-(Thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide287.

White solid (35.0 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.18(t, J=7.53 Hz, 3H), 7.46 (t, J=4.52 Hz, 1H), 7.78 (d, J=6.40 Hz, 1H),8.11-8.19 (m, 1H), 8.44 (d, J=6.27 Hz, 1H), 8.70 (d, J=2.89 Hz, 1H),8.78 (d, J=2.01Hz, 1H), 8.88 (s, 1H), 8.91(s, 1H), 9.14 (d, J=2.12 Hz,1H), 9.16 (d, J=2.13 Hz, 1H), 10.65 (s, 1H), 14.79 (brs, 1H), 14.87 (s,1H); ESIMS found for C₂₄H₁₈N₈OS m/z 467.1(M+1).

N,N-Dimethyl-5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine293.

White solid (65.4 mg, 0.15 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 3.09(s, 6H), 7.24 (dd, J=4.83, 3.70 Hz, 1H), 7.45 (d, J=5.52 Hz, 1H), 7.49(s, 1H), 7.72 (d, J=4.89 Hz, 1H), 8.23 (d, J=2.63 Hz, 1H), 8.32 (d,J=5.52 Hz, 1H), 8.37 (s, 1H), 8.71(d, J=2.63 Hz, 1H), 9.08 (d, J=2.13Hz, 1H), 9.15 (d, J=2.13 Hz, 1H), 13.77 (s, 1H), 14.53 (s, 1H); ESIMSfound for C₂₃H₁₈N₈S m/z 439.1(M+1).

N,N-Dimethyl-1-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine299.

White solid (25.0 mg, 0.06 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 2.82(d, J=2.76 Hz, 6H), 4.51(d, J=2.64 Hz, 2H), 7.45 (t, J=4.45 Hz, 1H),7.82 (d, J=6.27 Hz, 1H), 8.18 (d, J=4.64 Hz, 1H), 8.44 (d, J=6.27 Hz,1H), 8.70 (s, 1H), 8.82 (d, J=3.39 Hz, 1H), 8.91(s, 1H), 9.15-9.22 (m,3H), 11.19 (brs, 1H), 14.89 (brs, 1H), 14.92 (brs, 1H); ESIMS found forC₂₄H₂₀N₈S m/z 453.1(M+1).

N-(5-(3-(4-(Thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide305.

White solid (8.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm0.88-0.99 (m, 4H), 1.94-2.02 (m, 1H), 7.41-7.48 (m, 1H), 7.78 (d, J=6.27Hz, 1H), 8.10 (d, J=4.52 Hz, 1H), 8.42 (d, J=6.40 Hz, 1H), 8.75 (d,J=3.01Hz, 1H), 8.89 (brs, 2H), 8.90 (brs, 1H), 9.08-9.15 (m, 2H), 11.22(brs, 1H), 14.84 (brs, 1H), 14.88 (s, 1H); ESIMS found for C₂₅H₁₈N₈OSm/z 479.1(M+1).

5-(5-((3,3-Difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine311.

White solid (22.0 mg, 0.04 mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 2.25-2.40(m, 2H), 2.86 (t, J=6.96 Hz, 2H), 3.01(t, J=13.11Hz, 2H), 3.80 (s, 2H),7.09-7.16 (m, 1H), 7.25 (d, J=5.65 Hz, 1H), 7.54 (d, J=4.77 Hz, 1H),8.04-8.11(m, 2H), 8.36 (d, J=3.14 Hz, 1H), 8.55 (s, 1H), 8.73-8.82 (m,2H), 8.94 (d, J=2.01Hz, 1H); ESIMS found for C26H₂₀F₂N₈S m/z 515.1(M+1).

N-(5-(3-(4-(5-Fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide314.

White solid (9.4 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.00 (d,J=6.53 Hz, 6H), 2.17 (non, J=6.40 Hz, 1H), 2.32 (d, J=7.15 Hz, 2H), 6.94(dd, J=4.20, 1.82 Hz, 1H), 7.45 (d, J=5.52 Hz, 1H), 8.27 (d, J=5.40 Hz,1H), 8.30 (s, 1H), 8.42 (t, J=3.95 Hz, 1H), 8.69-8.74 (m, 2H), 8.78 (d,J=1.76 Hz, 1H), 9.08 (s, 2H), 10.35 (s, 1H); ESIMS found for C₂₆H₂₁FN₈OSm/z 513.1(M+1).

N-(5-(3-(4-(5-Fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide320.

White solid (15.2 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.31(s,9H), 6.93 (dd, J=4.08, 1.94 Hz, 1H), 7.45 (d, J=5.40 Hz, 1H), 8.28 (d,J=5.65 Hz, 1H), 8.43 (t, J=4.02 Hz, 1H), 8.68 (t, J=2.01Hz, 1H), 8.78(d, J=1.88 Hz, 1H), 8.89 (d, J=2.13 Hz, 1H), 9.06-9.12 (m, 2H), 9.65 (s,1H); ESIMS found for C₂₆H₂₁FN₈OS m/z 513.1(M+1).

5-(3-(4-(5-Methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine341.

White solid (32.0 mg, 0.08 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 2.63(s, 3H), 7.14 (d, J=2.64 Hz, 1H), 7.69 (d, J=6.27 Hz, 1H), 7.80-7.92 (m,2H), 7.99 (brs, 1H), 8.10 (s, 1H), 8.32 (d, J=6.40 Hz, 1H), 8.41(s, 1H),8.59 (d, J=3.51Hz, 1H), 8.85 (s, 1H), 14.41(s, 1H), 14.69 (brs, 1H);ESIMS found for C₂₂H₁₆N₈S m/z 425.0 (M+1).

N-(5-(3-(4-(5-Methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide347.

White solid (18.0 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.17(d, J=6.65 Hz, 7H), 2.56 (s, 3H), 7.12 (brs, 1H), 7.69 (d, J=4.77 Hz,1H), 8.31(d, J=5.27 Hz, 1H), 8.55 (brs, 1H), 8.76 (brs, 1H), 8.89 (brs,1H), 9.03 (brs, 1H), 9.08 (brs, 2H), 10.87 (brs, 1H), 14.83 (brs, 2H);ESIMS found for C₂₆H₂₂N₈OS m/z 495.2 (M+1).

N-(5-(3-(4-(5-Methylthiophen-2-yl)-1H-imidazo[4,5c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide359.

White solid (20.0 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm1.53-1.65 (m, 2H), 1.66-1.84 (m, 4H), 1.87-1.99 (m, 2H), 2.55 (s, 3H),2.94 (quin, J=7.87 Hz, 1H), 7.10 (d, J=3.26 Hz, 1H), 7.66 (d, J=6.40 Hz,1H), 8.29 (d, J=6.40 Hz, 1H), 8.51(d, J=3.64 Hz, 1H), 8.74 (s, 1H), 8.87(s, 1H), 9.01(d, J=2.01Hz, 1H), 9.05 (brs, 2H), 10.86 (brs, 1H), 14.78(brs, 2H); ESIMS found for C₂₈H₂₄N₈OS m/z 521.3 (M+1).

1-(5-(2-(5-(Pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one368.

White solid (12.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 2.64(s, 3H), 7.67 (d, J=5.14 Hz, 1H), 8.01-8.06 (m, 1H), 8.10 (d, J=3.26 Hz,1H), 8.44 (d, J=5.14 Hz, 1H), 8.70 (d, J=3.64 Hz, 1H), 8.74-8.81(m, 1H),8.85-8.94 (m, 1H), 9.19 (d, J=1.38 Hz, 1H), 9.26 (s, 1H), 9.36 (s, 1H),14.32 (s, 1H), 14.78 (s, 1H); ESIMS found for C₂₃H₁₅N₇OS m/z 438.1(M+1).

N-(5-(3-(4-(5-Acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide374.

White solid (9.0 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 2.63 (s,3H), 3.86 (s, 2H), 7.25-7.31(m, 1H), 7.35 (t, J=7.40 Hz, 2H), 7.39-7.43(m, 2H), 7.86 (d, J=4.77 Hz, 1H), 8.05 (d, J=3.89 Hz, 1H), 8.39 (d,J=4.14 Hz, 1H), 8.44 (d, J=6.15 Hz, 1H), 8.72 (s, 1H), 8.90 (brs, 1H),9.02 (s, 1H), 9.18 (brs, 1H), 9.31(brs, 1H); ESIMS found for C₃₁H₂₂N₈O₂Sm/z 571.2 (M+1).

N-(5-(3-(4-(5-Acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide380.

White solid (14.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.06(s, 9H), 2.33 (s, 2H), 2.58 (s, 3H), 7.60 (d, J=5.27 Hz, 1H), 8.08 (d,J=4.14 Hz, 1H), 8.41(d, J=5.40 Hz, 1H), 8.69-8.73 (m, 1H), 8.77 (d,J=3.89 Hz, 1H), 8.87 (d, J=5.52 Hz, 2H), 9.08 (d, J=2.26 Hz, 1H), 9.12(d, J=2.38 Hz, 1H), 10.43 (s, 1H), 14.06 (s, 1H), 14.70 (s, 1H); ESIMSfound for C₂₉H₂₆N₈O₂S m/z 551.2 (M+1).

N-(5-(3-(4-(5-Acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide386.

White solid (6.0 mg, 0.01mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 1.14-1.36(m, 3H), 1.40-1.52 (m, 2H), 1.63-1.70 (m, 1H), 1.74-1.81(m, 2H), 1.90(d, J=11.04 Hz, 2H), 2.05-2.09 (m, 1H), 2.56 (s, 3H), 7.65 (d, J=5.77Hz, 1H), 8.06 (d, J=3.89 Hz, 1H), 8.39 (d, J=5.77 Hz, 1H), 8.74 (d,J=3.89 Hz, 1H), 8.80 (brs, 1H), 8.96 (brs, 1H), 9.06 (s, 2H), 9.08 (brs,1H), 10.80 (brs, 1H), 14.35 (s, 1H), 14.80 (brs, 1H); ESIMS found forC₃₀H₂₆N₈O₂S m/z 563.2 (M+1).

N-(3-Fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide395.

White solid (12.0 mg, 0.02 mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 2.64 (s,3H), 2.80 (s, 3H), 4.36 (s, 2H), 7.50 (d, J=8.78 Hz, 1H), 8.02 (d,J=9.04 Hz, 1H), 8.09-8.15 (m, 2H), 8.44 (s, 1H), 8.58 (d, J=6.53 Hz,1H), 8.76-8.81(m, 2H), 8.88 (s, 1H), 9.04 (d, J=2.01Hz, 1H); ESIMS foundfor C₂₆H₂₁FN₈O₂S m/z 529.2 (M+1).

N-(5-(3-(4-(3-Fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide401.

White solid (16.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 2.87(s, 3H), 4.31(d, J=6.27 Hz, 2H), 7.31(d, J=8.66 Hz, 1H), 7.58-7.64 (m,2H), 7.65-7.70 (m, 1H), 7.76 (t, J=6.34 Hz, 1H), 7.88 (brs, 1H),8.03-8.07 (m, 2H), 8.48 (brs, 1H), 8.57 (d, J=6.02 Hz, 2H), 8.77 (s,1H), 8.92 (d, J=1.38 Hz, 1H), 9.10 (d, J=2.13 Hz, 1H), 9.12 (s, 1H),9.15 (d, J=1.63 Hz, 1H), 10.78 (s, 1H), 14.66 (brs, 1H), 14.84 (brs,1H); ESIMS found for C₃₂H₂₄FN₉O₃S m/z 634.1(M+1).

N-(5-(3-(4-(3-Fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide407.

White solid (10.0 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 0.96(t, J=7.34 Hz, 3H), 1.66 (sxt, J=7.28 Hz, 2H), 2.45 (t, J=7.28 Hz, 2H),2.86 (s, 3H), 4.33 (d, J=5.90 Hz, 2H), 7.51(d, J=9.03 Hz, 1H), 7.80 (t,J=6.15 Hz, 1H), 7.98 (d, J=6.27 Hz, 1H), 8.42 (d, J=9.03 Hz, 1H), 8.50(brs, 1H), 8.58 (d, J=6.27 Hz, 1H), 8.77 (s, 1H), 8.98 (s, 1H), 9.01(d,J=5.14 Hz, 2H), 9.12 (s, 1H), 11.04 (s, 1H), 14.96 (brs, 2H); ESIMSfound for C₂₉H₂₆FN₉O₃S m/z 600.2 (M+1).

N-(3-(2-(5-(5-((Benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide413.

White solid (31.4 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 2.93(s, 3H), 4.26 (t, J=5.46 Hz, 2H), 4.35-4.46 (m, 4H), 7.38-7.48 (m, 4H),7.54 (d, J=9.41Hz, 1H), 7.62 (dd, J=7.53, 1.76 Hz, 2H), 7.86 (t,J=6.21Hz, 1H), 8.02 (d, J=6.27 Hz, 1H), 8.51(brs, 2H), 8.61(d, J=6.27Hz, 1H), 8.84 (s, 1H), 8.92 (d, J=1.63 Hz, 1H), 9.13 (d, J=2.13 Hz, 1H),9.17 (d, J=2.13 Hz, 1H), 9.24 (d, J=1.88 Hz, 1H), 10.11(brs, 2H), 14.98(brs, 2H); ESIMS found for C₃₃H₂₈FN₉O₂S m/z 634.3 (M+1).

N-(3-Fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide416.

White solid (20.1mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 2.95 (s,3H), 4.38 (d, J=6.27 Hz, 2H), 7.53 (dd, J=10.67, 2.64 Hz, 1H), 7.82 (t,J=5.77 Hz, 1H), 7.97 (brs, 1H), 8.50 (brs, 2H), 8.60 (d, J=6.27 Hz, 1H),9.11-9.19 (m, 2H), 9.29 (s, 1H), 9.34 (s, 2H), 14.92 (brs, 2H); ESIMSfound for C₂₄H₁₈FN₉O₂S m/z 516.1(M+1).

N¹-(3-Fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine428.

White solid (26.0 mg, 0.05 mmol). ¹H NMR (CD₃OD, 400 MHz) δppm 1.33 (d,J=6.02 Hz, 6H), 2.98 (s, 6H), 3.47 (brs, 2H), 3.72 (brs, 2H), 3.81-3.94(m, 1H), 6.85 (d, J=10.79 Hz, 1H), 7.43 (brs, 1H), 7.92 (brs, 1H), 7.98(brs, 1H), 8.06-8.14 (m, 2H), 8.37 (s, 1H), 8.58 (dd, J=4.77, 1.00 Hz,1H), 9.01(s, 1H), 9.17 (brs, 1H); ESIMS found for C₃₀H₃₁FN₁₀ m/z 551.2(M+1).

N-(5-(3-(4-(3-((2-(Dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide434.

White solid (11.2 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm 0.91(t,J=7.34 Hz, 3H), 1.36 (sxt, J=7.40 Hz, 2H), 1.61(quin, J=7.50 Hz, 2H),2.11(s, 6H), 2.32 (t, J=6.34 Hz, 2H), 2.39 (t, J=7.40 Hz, 2H), 3.09-3.17(m, 2H), 5.86 (t, J=4.83 Hz, 1H), 6.48 (dt, J=11.70, 2.24 Hz, 1H), 7.53(d, J=5.40 Hz, 1H), 7.92-8.04 (m, 2H), 8.19 (s, 1H), 8.40-8.46 (m, 2H),8.72 (d, J=2.01Hz, 1H), 8.87 (d, J=2.26 Hz, 1H), 8.97 (d, J=2.13 Hz,1H), 9.07 (d, J=2.26 Hz, 1H), 10.28 (s, 1H), 13.80 (s, 1H), 14.58 (s,1H); ESIMS found for C₃₂H₃₃FN₁₀O m/z 593.3 (M+1).

N¹-(3-(2-(5-(5-(((Cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine440.

White solid (17.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 400 MHz) δppm1.20-1.34 (m, 2H), 1.44-1.65 (m, 4H), 1.75-1.87 (m, 2H), 2.24-2.36 (m,1H), 2.80-2.90 (m, 6H), 2.95 (d, J=3.64 Hz, 2H), 3.38 (brs, 2H),3.62-3.70 (m, 2H), 4.33 (brs, 2H), 6.81(d, J=11.80 Hz, 1H), 7.77-7.89(m, 1H), 8.00 (d, J=6.15 Hz, 1H), 8.56 (d, J=6.52 Hz, 1H), 8.76 (brs,1H), 8.90 (s, 1H), 9.11(d, J=1.13 Hz, 1H), 9.14-9.26 (m, 2H), 9.63 (brs,2H), 10.62 (brs, 1H), 14.95 (brs, 1H), 15.04 (brs, 1H); ESIMS found forC₃₄H₃₇FN₁₀ m/z 605.3 (M+1).

3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine885.

Yellow solid (6.0 mg, 0.01mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm1.61-1.74 (m, 2H), 1.93 (br d, J=13.72 Hz, 2H), 2.70 (br t, J=11.11Hz,2H), 2.90 (br t, J=12.08 Hz, 1H), 3.13 (br d, J=11.25 Hz, 2H), 7.27-7.34(m, 1H), 7.51(d, J=5.49 Hz, 1H), 7.57-7.65 (m, 1H), 8.37 (d, J=5.49 Hz,1H), 8.59 (d, J=2.20 Hz, 1H), 8.76-8.83 (m, 2H), 8.96 (br d, J=10.70 Hz,1H); ESIMS found for C₂₃H₂₀FN₇ m/z 414.2 (M+1).

3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine886.

Yellow solid (42.0 mg, 0.03 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm 2.64(br s, 2H), 3.12 (br t, J=5.35 Hz, 2H), 3.55 (br s, 2H), 6.52 (br s,1H), 7.31-7.39 (m, 1H), 7.56 (d, J=5.49 Hz, 1H), 7.58-7.67 (m, 1H), 8.47(d, J=5.49 Hz, 1H), 8.70 (br d, J=7.96 Hz, 1H), 8.91(s, 2H), 8.96 (br d,J=10.43 Hz, 1H); ESIMS found for C₂₃H₁₈FN₇ m/z 412.2 (M+1).

3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine887.

Yellow solid (4.0 mg, 0.01mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm 7.36(td, J=8.37, 2.20 Hz, 1H), 7.56 (d, J=5.49 Hz, 1H), 7.65 (td, J=7.96,6.59 Hz, 1H), 8.10 (br s, 1H), 8.37 (br s, 1H), 8.47 (d, J=5.49 Hz, 1H),8.72 (br d, J=7.68 Hz, 1H), 8.98-9.06 (m, 3H), 13.18 (br s, 1H), 13.77(br s, 1H), 14.36 (br s, 1H); ESIMS found for C₂₁H₁₃FN₈m/z 397.1(M+1).

3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine888.

Orange solid (7.1mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm 3.95 (s,3H), 7.33 (td, J=8.37, 2.47 Hz, 1H), 7.53 (d, J=5.21Hz, 1H), 7.60-7.68(m, 1H), 8.00 (s, 1H), 8.29 (s, 1H), 8.40 (d, J=5.49 Hz, 1H), 8.72 (brd, J=7.68 Hz, 1H), 8.93 (d, J=2.20 Hz, 1H), 8.99 (d, J=2.20 Hz, 1H),9.03 (br d, J=12.08 Hz, 1H); ESIMS found for C₂₂H₁₅FN₈ m/z 411.1(M+1).

5-(1,2-Dimethyl-1H-imidazol-5-yl)-3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine889.

Yellow solid (6.7 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm 2.44(s, 3H), 3.70 (s, 3H), 7.13 (s, 1H), 7.32 (td, J=8.23, 2.47 Hz, 1H),7.56 (d, J=5.49 Hz, 1H), 7.61(td, J=7.96, 6.59 Hz, 1H), 8.46 (d, J=5.49Hz, 1H), 8.72 (br d, J=7.14 Hz, 1H), 8.77-8.83 (m, 2H), 8.88 (d, J=2.20Hz, 1H), 13.82 (brs, 1H), 14.47 (br s, 1H); ESIMS found for C₂₃H₁₇FN₈m/z 425.2 (M+1).

1-(6-(3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine890.

Yellow solid (5.9 mg, 0.01mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm3.72-3.79 (m, 2H), 3.93 (br t, J=6.60 Hz, 1H), 4.32 (br t, J=7.55 Hz,2H), 7.25 (t, J=8.53 Hz, 1H), 7.46 (br d, J=5.21Hz, 1H), 7.52-7.61(m,1H), 7.85 (s, 1H), 8.24 (d, J=4.65 Hz, 1H), 8.53 (s, 1H), 8.86 (br d,J=7.68 Hz, 1H), 8.90 (br d, J=11.53 Hz, 1H), 9.16 (br s, 1H), 9.44 (brs, 1H); ESIMS found for C₂₅H₁₉FN₁₀ m/z 479.2 (M+H).

5-(5-(Cyclohexyloxy)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine891.

Off-white solid (56 mg, 0.105 mmol, 47.7% yield). ¹H NMR (DMSO -d₆, 500MHz) δppm 1.25-1.36 (m, 1H), 1.36-1.47 (m, 2H), 1.48-1.61(m, 3H), 1.68-1.80 (m, 2H), 1.96-2.06 (m, 2H), 4.60-4.70 (m, 1H), 7.30(td, J=8.37,2.20 Hz, 1H), 7.54-7.64 (m, 2H), 7.86 (t, J=2.33 Hz, 1H), 8.38 (d,J=2.74 Hz, 1H), 8.47 (d, J=5.21Hz, 1H), 8.63 (d, J=1.65 Hz, 1H), 8.76(br d, J=7.96 Hz, 1H), 8.85 (br d, J=11.53 Hz, 1H), 9.09 (d, J=2.20 Hz,1H), 9.14 (d, J=2.20 Hz, 1H), 13.85 (brs, 1H), 14.54 (brs, 1H); ESIMSfound for C₂₉H₂₄FN₇O m/z 506.2 (M+1).

3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine892.

White solid (16 mg, 0.030 mmol, 33.4% yield). ¹H NMR (DMSO-d₆, 500 MHz)δppm 1.51-1.63 (m, 2H), 2.02 (br dd, J=8.64, 3.98 Hz, 2H), 2.60-2.68 (m,2H), 3.00 (dt, J=12.76, 4.19 Hz, 2H), 4.72 (dt, J=8.64, 4.46 Hz, 1H),7.31(td, J=8.44, 2.06 Hz, 1H), 7.53-7.63 (m, 2H), 7.88 (t, J=2.20 Hz,1H), 8.39 (d, J=2.74 Hz, 1H), 8.45 (d, J=5.49 Hz, 1H), 8.64 (d, J=1.65Hz, 1H), 8.77 (d, J=7.96 Hz, 1H), 8.85 (br d, J=10.43 Hz, 1H), 9.07 (d,J=2.20 Hz, 1H), 9.15 (d, J=2.20 Hz, 1H); ESIMS found for C₂₈H₂₃FN₈O m/z507.2 (M+1).

N-(5-(3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide893.

Yellow solid (11.3 mg, 0.02 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm1.08-1.29 (m, 2H), 1.67 (br d, J=14.00 Hz, 1H), 2.32 (br d, J=6.86 Hz,1H), 2.95 (br d, J=12.62 Hz, 1H), 7.17-7.31(m, 1H), 7.51(d, J=4.40 Hz,1H), 7.60 (br s, 1H), 8.35 (br s, 1H), 8.52 (br d, J=17.84 Hz, 1H), 8.74(br s, 1H), 8.77-8.89 (m, 3H), 8.92 (br s, 1H), 9.12 (br d, J=5.21Hz,1H), 10.28-10.40 (m, 1H); ESIMS found for C₃₀H₂₆FN₉O m/z 548.3 (M+1).

3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine894.

Beige solid (9 mg, 0.016 mmol, 66.2% yield). ¹H NMR (DMSO-d₆, 500 MHz)δppm 1.69 (dt, J=6.72, 3.22 Hz, 4H), 2.55 (br s, 4H), 2.87 (t, J=5.90Hz, 2H), 4.30 (t, J=5.90 Hz, 2H), 7.30 (td, J=8.30, 2.61Hz, 1H),7.54-7.64 (m, 2H), 7.89 (t, J=2.20 Hz, 1H), 8.40 (d, J=2.74 Hz, 1H),8.47 (d, J=5.49 Hz, 1H), 8.66 (d, J=1.65 Hz, 1H), 8.75 (br d, J=7.14 Hz,1H), 8.86 (br d, J=11.25 Hz, 1H), 9.10 (d, J=2.20 Hz, 1H), 9.16 (d,J=2.20 Hz, 1H), 13.83 (brs, 1H), 14.52 (brs, 1H); ESIMS found forC₂₉H₂₅FN₈O m/z 521.2 (M+1).

2-((5-(3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine895.

Yellow solid (1.9 mg, 0.004 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm 2.25(s, 6H), 2.71(t, J=5.76 Hz, 2H), 4.28 (t, J=5.76 Hz, 2H), 7.29 (td,J=8.30, 2.33 Hz, 1H), 7.53-7.64 (m, 2H), 7.88 (t, J=2.20 Hz, 1H), 8.39(d, J=2.74 Hz, 1H), 8.44 (br d, J=5.21Hz, 1H), 8.66 (d, J=1.65 Hz, 1H),8.77 (br d, J=7.41Hz, 1H), 8.88 (br d, J=10.15 Hz, 1H), 9.07 (d, J=1.92Hz, 1H), 9.16 (d, J=2.20 Hz, 1H); ESIMS found for C₂₇H₂₃FN₈O m/z 495.2(M+1).

3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine896.

Orange solid (16.8 mg, 0.04 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm 3.98(s, 3H), 7.32 (td, J=8.23, 2.20 Hz, 1H), 7.55-7.64 (m, 2H), 7.84-7.90(m, 1H), 8.40 (d, J=2.74 Hz, 1H), 8.47 (d, J=5.21Hz, 1H), 8.66 (d,J=1.92 Hz, 1H), 8.73 (br d, J=7.68 Hz, 1H), 8.87 (br d, J=10.70 Hz, 1H),9.10 (d, J=2.20 Hz, 1H), 9.15 (d, J=1.92 Hz, 1H), 13.81(br s, 1H), 14.54(br s, 1H); ESIMS found for C₂₄H₁₆FN₇O m/z 438.1(M+1).

5-(3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol897.

Yellow solid (4.6 mg, 0.01mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm 5.38 (brs, 1H), 7.33 (td, J=8.23, 2.47 Hz, 1H), 7.55-7.65 (m, 3H), 8.25 (d,J=2.74 Hz, 1H), 8.47 (d, J=5.21Hz, 1H), 8.54 (d, J=1.92 Hz, 1H), 8.78(br d, J=7.68 Hz, 1H), 8.83 (br d, J=11.80 Hz, 1H), 9.02 (d, J=2.20 Hz,1H), 9.11(d, J=2.20 Hz, 1H), 10.19 (br s, 1H), 13.83 (br s, 1H), 14.46(br s, 1H); ESIMS found for C₂₃H₁₄FN₇O miz 424.1(M+1).

5-(5-(Benzyloxy)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine898.

Yellow solid (37 mg, 0.068 mmol, 66.0% yield). ¹H NMR (DMSO-d₆, 500 MHz)δppm 5.33 (s, 2H), 7.22 (td, J=8.16, 2.33 Hz, 1H), 7.35-7.41(m, 1H),7.42 -7.48 (m, 2H), 7.52-7.62 (m, 4H), 7.98 (t, J=2.33 Hz, 1H),8.42-8.51(m, 2H), 8.70 (d, J=1.65 Hz, 1H), 8.75 (d, J=7.68 Hz, 1H), 8.85(br d, J=11.25 Hz, 1H), 9.11(d, J=2.20 Hz, 1H), 9.17 (d, J=1.92 Hz, 1H),13.83 (br s, 1H), 14.55 (br s, 1H); ESIMS found for C₃₀H₂₀FN₇O m/z 514.2(M+1).

2-Cyclohexyl-N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide899.

Light yellow solid (24 mg, 0.042 mmol, 36.5% yield). ¹H NMR (DMSO-d₆,500 MHz) δppm 0.97-1.08 (m, 2H), 1.12-1.31(m, 3H), 1.63 (br d, J=11.53Hz, 1H), 1.68 (br d, J=12.62 Hz, 2H), 1.75 (br d, J=10.70 Hz, 2H), 1.83(ddd, J=10.84, 7.27, 3.57 Hz, 1H), 2.30 (d, J=7.14 Hz, 2H), 7.21-7.30(m, 1H), 7.58 (d, J=5.21Hz, 1H), 7.61-7.69 (m, 1H), 8.48 (d, J=5.21Hz,1H), 8.60 (s, 1H), 8.74 (d, J=1.92 Hz, 1H), 8.76-8.86 (m, 3H), 9.02 (d,J=2.20 Hz, 1H), 9.09 (d, J=1.65 Hz, 1H), 10.29 (s, 1H), 13.87 (br s,1H), 14.58 (s, 1H); ESIMS found for C₃₁H₂₇FN₈O m/z 547.2 (M+1).

3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine900.

Off-white solid (20.0 mg, 0.05 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm7.37 (td, J=8.30, 2.61Hz, 1H), 7.56 (d, J=5.49 Hz, 1H), 7.60-7.68 (m,1H), 7.84 -7.91(m, 3H), 8.00 (dd, J=8.78, 1.65 Hz, 1H), 8.47 (d, J=5.49Hz, 1H), 8.69-8.76 (m, 3H), 9.01(br d, J=11.25 Hz, 1H), 9.11(s, 1H),13.75 (s, 1H), 14.01(s, 1H); ESIMS found for C₂₃H₁₄FN₇ m/z 408.1(M+1).

3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine901.

Off-white solid (35 mg, 0.082 mmol, 38.2% yield). ¹H NMR (DMSO -d₆, 500MHz) δppm 7.35 (td, J=8.30, 2.06 Hz, 1H), 7.44-7.51(m, 1H), 7.57 (d,J=5.49 Hz, 1H), 7.60-7.69 (m, 1H), 8.00 (td, J=7.68, 1.92 Hz, 1H), 8.18(d, J=7.96 Hz, 1H), 8.47 (d, J=5.49 Hz, 1H), 8.74-8.83 (m, 2H), 8.93 (brd, J=11.53 Hz, 1H), 9.42 (d, J=2.20 Hz, 1H), 9.63 (d, J=1.92 Hz, 1H),13.84 (br s, 1H), 14.51(br s, 1H); ESIMS found for C₂₃H₁₄FN₇ m/z408.1(M+1).

3-(4-(3-Fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine902.

Yellow solid (5-(mg, 0.126 mmol, 51.6% yield). ¹H NMR (DMSO-d₆, 500 MHz)δppm 7.33 (td, J=8.30, 2.06 Hz, 1H), 7.55 (d, J=5.21Hz, 1H), 7.62 (td,J=7.96, 6.59 Hz, 1H), 8.46 (d, J=5.21Hz, 1H), 8.71(d, J=2.47 Hz, 1H),8.76 (br d, J=6.86 Hz, 1H), 8.82 (dd, J=2.47, 1.65 Hz, 1H), 8.88 (br d,J=10.15 Hz, 1H), 9.45 (dd, J=3.43, 1.78 Hz, 2H), 9.65 (d, J=1.92 Hz,1H), 13.93 (br s, 1H), 14.43 (br s, 1H); ESIMS found for C₂₂H₁₃FN₈ m/z409.1(M+1).

N-(5-(3-(4-(3-(2-(Dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide1192.

Yellow solid (10 mg, 0.017 mmol, 26.6% yield). ¹H NMR (DMSO-d₆, 500 MHz)δppm 0.96 (d, J=6.59 Hz, 6H), 2.04-2.18 (m, 7H), 2.27 (d, J=7.14 Hz,2H), 2.42 (br s, 2H), 4.10 (t, J=5.63 Hz, 2H), 6.85-6.93 (m, 1H), 7.57(d, J=5.21Hz, 1H), 8.31(br d, J=10.70 Hz, 1H), 8.43-8.53 (m, 3H),8.71(d, J=2.20 Hz, 1H), 8.88 (d, J=2.47 Hz, 1H), 8.98 (d, J=2.20 Hz,1H), 9.05 (d, J=2.20 Hz, 1H), 10.27 (s, 1H), 13.85 (br s, 1H), 14.58 (brs, 1H); ESIMS found for C₃₂H₃₂FN₉O₂ m/z 594.3 (M+1).

N-(5-(3-(4-(3-Fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide1236.

Yellow solid (11.4 mg, 0.018 mmol, 30.1% yield). ¹H NMR (DMSO -d₆, 500MHz) δppm 0.97 (d, J=6.59 Hz, 6H), 1.59 (dt, J=6.66, 3.12 Hz, 4H),2.05-2.17 (m, 1H), 2.27 (d, J=7.41Hz, 2H), 2.37 (br s, 4H), 2.56 (t,J=5.76 Hz, 2H), 4.12 (t, J=5.76 Hz, 2H), 6.88 (dt, J=10.57, 2.26 Hz,1H), 7.57 (d, J=5.21Hz, 1H), 8.30 (br d, J=10.15 Hz, 1H), 8.43-8.48 (m,2H), 8.52 (br s, 1H), 8.71(d, J=1.92 Hz, 1H), 8.88 (d, J=2.47 Hz, 1H),8.97 (d, J=1.92 Hz, 1H), 9.06 (d, J=2.20 Hz, 1H), 10.28 (s, 1H), 14.23(brs, 1H); ESIMS found for C₃₄H₃₄FN₉O₂ m/z 620.3 (M+1).

N-(5-(3-(4-(3-Fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide1280.

Yellow solid (13.8 mg, 0.026 mmol, 20.3% yield). ¹H NMR (DMSO -d₆, 500MHz) δppm 0.98 (d, J=6.59 Hz, 6H), 2.12 (dquin, J=13.64, 6.81, 6.81,6.81, 6.81Hz, 1H), 2.28 (d, J=7.14 Hz, 2H), 6.64 (br d, J=10.15 Hz, 1H),7.55 (d, J=5.21Hz, 1H), 8.20 (s, 1H), 8.36 (br d, J=10.98 Hz, 1H),8.42-8.48 (m, 2H), 8.75 (d, J=1.65 Hz, 1H), 8.87 (d, J=2.20 Hz, 1H),9.00 (d, J=2.20 Hz, 1H), 9.13 (d, J=1.92 Hz, 1H), 9.99 (s, 1H), 10.23(s, 1H), 13.82 (s, 1H), 14.57 (s, 1H); ESIMS found for C₂₈H₂₃FN₈O₂ m/z523.2 (M+1).

N-(5-(3-(4-(3-Fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide1324.

Yellow solid (49.3 mg, 0.092 mmol, 73.1% yield). ¹H NMR (DMSO -d₆, 500MHz) δppm 0.97 (d, J=6.59 Hz, 6H), 2.11(dquin, J=13.67, 6.67, 6.67,6.67, 6.67 Hz, 1H), 2.28 (d, J=7.14 Hz, 2H), 3.83 (s, 3H), 6.89 (dt,J=10.43, 2.33 Hz, 1H), 7.57 (d, J=5.49 Hz, 1H), 8.31(br d, J=9.61Hz,1H), 8.44-8.50 (m, 2H), 8.59 (s, 1H), 8.72 (d, J=1.92 Hz, 1H), 8.87 (d,J=2.20 Hz, 1H), 8.98 (d, J=2.20 Hz, 1H), 9.09 (d, J=2.20 Hz, 1H), 10.27(s, 1H), 13.86 (br s, 1H), 14.58 (s, 1H); ESIMS found for C₂₉H₂₅FN₈O₂m/z 537.2 (M+1).

2-(Dimethylamino)-N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide1367.

Yellow solid (17 mg, 0.007 mmol). ¹H NMR (DMSO-d₆, 500 MHz) δppm 2.35(s, 6H), 3.20 (s, 2H), 7.25-7.33 (m, 1H), 7.57 (d, J=5.21Hz, 1H),7.61-7.69 (m, 1H), 8.48 (d, J=5.49 Hz, 1H), 8.63 (s, 1H), 8.76-8.85 (m,3H), 8.96 (d, J=2.20 Hz, 1H), 9.04 (d, J=2.20 Hz, 1H), 9.12 (d, J=2.20Hz, 1H), 10.15 (s, 1H), 13.84 (br s, 1H), 14.57 (br s, 1H); ESIMS foundfor C₂₇H₂₂FN₉₀ m/z 508.2 (M+1).

Example 2

The screening assay for Wnt activity is described as follows. Reportercell lines can be generated by stably transducing cancer cell lines(e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells)with a lentiviral construct that includes a Wnt-responsive promoterdriving expression of the firefly luciferase gene.

SW480 colon carcinoma cells were transduced with a lentiviral vectorexpressing luciferase with a human Sp5 promoter consisting of a sequenceof eight TCF/LEF binding sites. SW480 cells stably expressing theSp5-Luc reporter gene and a hygromycin resistance gene were selected bytreatment with 150 μg/ml of hygromycin for 7 days. These stablytransduced SW480 cells were expanded in cell culture and used for allfurther screening activities. For Sp5-Luc reporter gene assays, thecells were plated at 10,000 cells/well in 96-well plates with growthmedium containing 10% fetal calf serum and incubated overnight at 37° C.and 5% CO₂. Each compound was dissolved in DMSO as a 10 mM stock instandard j-vials and used to prepare compound source plates indose-response format with 3-fold serial dilutions and a 10 mM topconcentration. Compound transfer from serially diluted source plates toassay plates containing the cells was accomplished using a pintool(Multimek 96, Beckman equipped with V&P Scientific FP1S50H pins) basedliquid handling protocol. This protocol used a slotted pin to transfer50 nl of compound from a source plate well to an assay plate wellcontaining 50 μl of cells in growth medium. The 1000-fold dilutionresulted in a final DMSO concentration of 0.1% on the cells in eachwell. Control wells received 50 nl of DMSO treatment for normalizationand calculating ICso values. The treated cells were incubated at 37° C.and 5% CO₂ for an additional forty-two hours. Following incubation, thegrowth medium was removed and 50 μl of BrightGlo luminescence reagent(Promega) was added to each well of the 96-well assay plates. The plateswere placed on an orbital shaker for 5 min and then luminescence wasquantified on the Victor3 (Perkin Elmer) plate reader. Readings werenormalized to DMSO only treated cells, and normalized activities wereutilized for ICso calculations using the dose-response log (inhibitor)vs. response—variable slope (four parameters) nonlinear regressionfeature available in GraphPad Prism 5.0 or 6.0. Table 2 shows themeasured activity for selected compounds of Formula I as describedherein.

TABLE 2 Compound IC₅₀ (μM) 1 0.0058 7 0.0353 13 0.3388 19 0.005 250.0339 28 0.0377 34 0.1522 40 >10 46 0.005 52 0.1546 55 0.0059 61 0.02868 0.0957 73 0.0602 82 0.0419 87 >10 90 0.0797 93 3.8830 101 >10 109 >10114 >10 121 >10 126 1.1160 136 >10 141 >10 148 6.155 157 0.1484 1630.7769 169 2.2720 175 0.413 181 0.2432 184 0.0048 190 1.5760 196 0.5793211 0.3340 217 0.6728 223 >10 229 1.5490 234 0.1791 239 0.018 245 0.1016251 0.0099 257 0.3094 266 0.3391 272 0.013 278 0.056 284 0.8750 2870.0229 293 0.0371 299 1.4410 305 0.009 311 0.0228 314 0.0063 320 0.0093341 0.0009 347 0.0208 353 0.5755 359 0.0299 368 0.0104 374 >10 3860.1878 395 0.008 401 >10 407 0.0741 413 0.1432 416 >10 428 0.015 4340.0219 440 0.7520 885 3.865 886 3.700 887 0.006 888 0.012 889 0.012 8900.365 891 0.935 892 0.315 893 0.868 894 1.500 895 0.343 896 0.037 8970.023 898 3.265 899 1.970 900 >10 901 >10 902 0.705 1192 0.400 12360.445 1280 0.090 1324 0.085 1367 0.183

Example 3

The above synthesized compounds were screened using primary humanmesenchymal stem cells (hMSCs) to determine their ability to inducechondrogenesis (process by which cartilage is developed).

Human Mesenchymal Stem Cell Culture: Primary human mesenchymal stemcells (hMSCs) were purchased from Lonza (Walkersville, Md.) and expandedin Mesenchymal Stem Cell Growth Media (Lonza). Cells between passage 3and 6 were used for the experiments.

Compound Screening: Each compound was dissolved in DMSO as a 10 mM stockand used to prepare compound source plates. Serial dilution (1:3,6-point dose-response curves from 2700 nM to 10 nM) and compoundtransfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.)into 96-well clear bottom assay plates (Greiner Bio-One) withappropriate DMSO backfill for a final DMSO concentration of 0.03%. hMSCswere plated at 20,000 cells/well in 250 μL/well Incomplete ChondrogenicInduction Medium (Lonza; DMEM, dexamethasone, ascorbate,insulin-transferrin-selenium [ITS supplement], gentamycin -amphotericin[GA-1000], sodium pyruvate, proline and L-glutamine). TGF-β3 (10 ng/mL)was used as a positive control for differentiation while negativecontrol wells were treated with 75 nL DMSO for normalization andcalculating EC₅₀ values. Cells were incubated at 37° C. and 5% CO₂ for 6days. To image chondrogenic nodules, the cells were fixed using 4%formaldehyde (Electron Microscopy Sciences), and stained with 2 μg/mLRhodamine B (Sigma-Aldrich) and 20 μM Nile Red (Sigma-Aldrich) [JohnsonK., et.al, A Stem Cell—Based Approach to Cartilage Repair, Science,(2012), 336(6082), 717-721]. The nodules imaged (4 images per well at 4Xmagnification) by excitation at 531nm and emission at 625 nm andquantified using the CellInsight CX5 (Thermo Scientific). Number ofnodules in each well was normalized to the average of 3 DMSO treatedwells on the same plate using Excel (Microsoft Inc.). The normalizedaverages (fold change over DMSO) of 3 replicate wells for each compoundconcentration were calculated. Due to solubility limitations of some ofthe compounds, curve fitting was incomplete leading to inaccurate EC₅₀determinations.

Using TGF-β3 as a positive control, the concentration of test compoundsrequired to induce equivalent levels of chondrogenesis is reported. Inaddition, the maximum activity of each compound and the respective dosethat each compound reached maximum chondrogenesis activity is reported.Table 3 shows the activity of selected compounds as provided herein.

TABLE 3 Conc Conc Max. (nM) of (nM) of Activity as 100% Max. % TGF-β3TGF-β3 Compound activity activity activity 1 2700 300 117.0 46 900 90080.6 55 2700 N/A 32.2 184 100 N/A 5.4 251 900 N/A 52.8 272 30 30 72.0305 10 N/A 54.9 341 2700 N/A 58.2 368 30 30 84.6 395 10 10 92.8 428 3030 82.9 888 30 30 74.9 889 100 100 151.7

Example 4

The above synthesized compounds were screened using primary humanfibroblasts (derived from IPF patients) treated with TGF-β1to determinetheir ability to inhibit the fibrotic process.

Human Fibroblast Cell Culture: Primary human fibroblasts derived fromIPF patients (LL29 cells) [¹Xiaoqiu Liu, et.al., “Fibrotic LungFibroblasts Show Blunted Inhibition by cAMP Due to Deficient cAMPResponse Element-Binding Protein Phosphorylation”, Journal ofPharmacology and Experimental Therapeutics (2005), 315(2), 678-687;²Watts, K. L., et.al., “RhoA signaling modulates cyclin D1expression inhuman lung fibroblasts; implications for idiopathic pulmonary fibrosis”,Respiratory Research (2006), 7(1), 88]were obtained from American TypeCulture Collection (ATCC) and expanded in F12 medium supplemented with15% Fetal Bovine Serum and Penicillin/Streptomycin.

Compound Screening: Each compound was dissolved in DMSO as a 10 mM stockand used to prepare compound source plates. Serial dilution (1:2,11-point dose-response curves from 10 μM to 1.87 nM) and compoundtransfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.)into 384-well clear bottom assay plates (Greiner Bio-One) withappropriate DMSO backfill for a final DMSO concentration of 0.1%. LL29cells were plated at 1,500 cells/well in 80 μl/well F12 mediumsupplemented with 1% Fetal Bovine Serum. One hour after addition of thecells, TGF-β1(Peprotech; 20 ng/mL) was added to the plates to inducefibrosis (ref 1and 2 above). Wells treated with TGF-β1and containingDMSO were used as controls. Cells were incubated at 37° C. and 5% CO₂for 4 days. Following incubation for 4 days, SYTOX green nucleic acidstain (Life Technologies [Thermo Fisher Scientific]) was added to thewells at a final concentration of luM and incubated at room temperaturefor 30 min. Cells were then fixed using 4% formaldehyde (ElectronMicroscopy Sciences), washed 3 times with PBS followed by blocking andpermeabilization using 3% Bovine Serum Albumin (BSA; Sigma) and 0.3%Triton X-100 (Sigma) in PBS. Cells were then stained with antibodyspecific to α-smooth muscle actin (αSMA; Abcam) (ref 1and 2 above) in 3%Bovine Serum Albumin (BSA; Sigma) and 0.3% Triton X-100 (Sigma) in PBS,and incubated overnight at 4° C. Cells were then washed 3 times withPBS, followed by incubation with Alexa Flor-647 conjugated secondaryantibody (Life Technologies [Thermo Fisher Scientific]) and DAPI at roomtemperature for 1hour. Cells were then washed 3 times with PBS andplates were sealed for imaging. αSMA staining was imaged by excitationat 630 nm and emission at 665 nm and quantified using the CompartmentalAnalysis program on the CellInsight CX5 (Thermo Scientific). Dead orapoptotic cells were excluded from analysis based on positive SYTOXgreen staining. % of total cells positive for αSMA were counted in eachwell and normalized to the average of 11wells treated with TGF-β1on thesame plate using Dotmatics' Studies Software. The normalized averages(fold change over untreated) of 3 replicate wells for each compoundconcentration were used to create dose-responses curves and EC₅₀ valueswere calculated using non-linear regression curve fit in the Dotmatics'Studies Software. The EC₅₀values are reported.

Table 4 shows the activity of selected compounds as provided herein.

TABLE 4 Inhibition of fibrosis Compound EC₅₀ (nM) 1 0.062 7 0.365 130.030 19 0.027 28 0.881 34 3.060 40 9.990 46 0.253 55 0.283 61 >10 680.930 73 0.611 87 0.009 90 9.990 101 9.990 109 9.990 114 9.990 121 9.990136 0.009 141 9.990 148 0.009 163 0.009 169 0.888 175 0.859 181 1.130196 9.990 211 9.990 223 9.990 239 0.024 245 0.280 251 0.073 257 0.244272 0.009 284 1.183 287 0.578 293 0.009 299 9.990 311 0.174 314 0.009320 0.009 341 0.009 347 0.633 359 4.849 368 0.241 374 0.427 386 0.053395 0.009 401 9.990 416 9.990 428 0.020 434 0.013 440 0.858 885 0.009887 0.010 888 0.014 889 0.009 890 0.205 892 0.009 893 0.308 895 9.990896 0.108 900 0.009 902 0.009

What is claimed is:
 1. A method of treating a disorder selected from thegroup consisting of: skin fibrosis; scleroderma; progressive systemicfibrosis; muscle fibrosis; glomerulosclerosis; glomerulonephritis;hypertrophic scar formation; uterine fibrosis; renal fibrosis; cirrhosisof the liver; liver fibrosis; adhesions occurring in the abdomen,pelvis, spine or tendons; chronic obstructive pulmonary disease;fibrosis following myocardial infarction; pulmonary fibrosis; idiopathicpulmonary fibrosis (IPF); fibrosis and scarring associated withdiffuse/interstitial lung disease; central nervous system fibrosis;fibrosis following stroke; fibrosis associated with neuro-degenerativedisorders selected from the group consisting of Alzheimer's Disease andmultiple sclerosis, fibrosis associated with proliferativevitreoretinopathy (PVR); restenosis; endometriosis; ischemic disease;and radiation fibrosis in a subject, the method comprising administeringto the subject a therapeutically effective amount of a compound ofFormula I, or a pharmaceutically acceptable salt thereof:

wherein: R¹is selected from the group consisting of —heteroaryl(R⁴)_(q)and —heterocyclyl(R⁵)_(h); R² is selected from the group consisting of Hand halide; R³ is selected from the group consisting of—heteroaryl(R⁶)_(q), —heterocyclyl(R⁷), and —aryl(R⁸)_(k); each R⁴ isone substituent attached to the heteroaryl and is independently selectedfrom the group consisting of halide, —(C₁₋₆ alkyl), —(C₁₋₄alkylene)_(p)heterocyclyl(R⁹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R¹⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹¹)_(k),—NHC(═O)R¹², —NR¹³R¹⁴, —(C₁₋₆ alkylene)NR¹⁵R^(16,) and —OR²²; each R⁵ isone substituent attached to the heterocyclyl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN; each R⁶ is one substituent attached to the heteroaryl and isindependently selected from the group consisting of —(C₁₋₆ alkyl),halide, —CF₃, —OCH₃, —CN, and —C(═O)R¹⁷; each R⁷ is one substituentattached to the heterocyclyl and is independently selected from thegroup consisting of —(C₁₋₆ alkyl), halide, —CF₃, —CN, and —OCH₃; each R⁸is one substituent attached to the aryl and is independently selectedfrom the group consisting of —(C₁₋₆ alkyl), halide, —CF₃, —CN, —OCH₃,—(C₁₋₆ alkylene)_(p)NHSO₂R¹⁷, —NR¹³(C₁₋₆ alkylene)NR¹³R¹⁴, —(C₁₋₆alkylene)_(p)NR¹³R¹⁴; and —OR²⁵; each R⁹ is one substituent attached tothe heterocyclyl and is independently selected from the group consistingof amino, —(C₁₋₄ alkyl), halide, —CF₃, and —CN; each R¹⁰ is onesubstituent attached to the carbocyclyl and is independently selectedfrom the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and —CN; eachR¹¹is one substituent attached to the aryl and is independently selectedfrom the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and —CN; eachR¹² is independently selected from the group consisting of —(C₁₋₉alkyl), —heteroaryl(R¹⁸)_(q), —aryl(R¹⁹)_(k), —CH₂aryl(R¹⁹)_(k),—carbocyclyl(R²⁰)_(j), —CH₂carbocyclyl(R²⁰)_(j), —(C₁₋₄alkylene)_(p)NR²³R²⁴, —heterocyclyl(R²¹)_(h), and—CH₂heterocyclyl(R²¹)_(h); each R¹³ is independently selected from thegroup consisting of H and —(C₁₋₆ alkyl); each R¹⁴ is independentlyselected from the group consisting of H, —(C₁₋₆ alkyl),—CH₂aryl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j); each R¹⁵ isindependently selected from the group consisting of H and —(C₁₋₆ alkyl);each R¹⁶ is independently selected from the group consisting of H,—(C₁₋₆ alkyl), —CH₂aryl(R¹⁹)_(k), and —CH₂carbocyclyl(R²⁰)_(j); each R¹⁷is a —(C₁₋₆ alkyl); each R¹⁸ is one substituent attached to theheteroaryl and is independently selected from the group consisting of—(C₁₋₄ alkyl), halide, —CF₃, and —CN; each R¹⁹ is one substituentattached to the aryl and is independently selected from the groupconsisting of —(C₁₋₄ alkyl), halide, —CF₃, and —CN; each R²⁰ is onesubstituent attached to the carbocyclyl and is independently selectedfrom the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and —CN; eachR²¹is one substituent attached to the heterocyclyl and is independentlyselected from the group consisting of —(C₁₋₄ alkyl), halide, —CF₃, and—CN; R²² is selected from the group consisting of H, —(C₁₋₆ alkyl),—(C₁₋₄ alkylene)_(p)heterocyclyl(R²¹)_(h), —(C₁₋₄alkylene)_(p)carbocyclyl(R²⁰)_(j), —(C₁₋₄ alkylene)_(p)aryl(R¹⁹)_(k),and —(C₁₋₆ alkylene)_(p)NR23R²⁴; each R²³ is independently selected fromthe group consisting of H and —(C₁₋₆ alkyl); each R²⁴ is independentlyselected from the group consisting of H and —(C₁₋₆ alkyl); R²⁵ isselected from the group consisting of H, —(C₁₋₆ alkyl), —(C₁₋₄alkylene)_(p)heterocyclyl(R²¹)_(h), and —(C₁₋₆ alkylene)_(p)NR²³R²⁴;each p is independently 0 or 1; each q is independently 0 to 4; each his independently 0 to 10; each k is independently 0 to 5; and each j isindependently 0 to
 12. 2. The method of claim 1, wherein R¹is—heteroaryl(R⁴)_(q).
 3. The method of claim 2, wherein R¹is selectedfrom the group consisting of —pyridinyl(R⁴)_(q), —pyrimidinyl(R⁴)_(q),—pyrazolyl(R⁴)_(q), and —imidazolyl(R⁴)_(q).
 4. The method of claim 2,wherein q is 0, 1or
 2. 5. The method of claim 3, wherein R⁴ is selectedfrom the group consisting of —(C1-3 alkyl), —CH₂heterocyclyl(R⁹)_(h),—NHC(═O)R¹², —NR13R¹⁴; —CH₂NR¹⁵R^(16,) and —OR²².
 6. The method of claim1, wherein R³ is —aryl(R⁸)k.
 7. The method of claim 6, wherein R³ is—phenyl(R⁸)k.
 8. The method of claim 7, wherein k is 1or
 2. 9. Themethod of claim 8, wherein each R⁸ is independently selected from thegroup consisting of halide and —CH₂NHSO₂R¹⁷.
 10. The method of claim 1,wherein R³ is —heteroaryl(R⁶)_(q).
 11. The method of claim 10, whereinR³ is selected from the group consisting of —pyridinyl(R⁶)_(q),—imidazolyl(R⁶)_(q), —furanyl(R⁶)_(q), and —thiophenyl(R⁶)_(q).
 12. Themethod of claim 11, wherein q is 0 or
 1. 13. The method of claim 11,wherein q is 1and R⁶ is selected from the group consisting of halide,—(C₁₋₃ alkyl), and —C(═O)R¹⁷.
 14. The method of claim 1, wherein R³ is—heterocyclyl(R⁷)_(h).
 15. The method of claim 14, wherein R³ isselected from the group consisting of —piperidinyl(R⁷)_(h),—morpholinyl(R⁷)_(h), and —piperazinyl(R⁷)_(h).
 16. The method of claim15, wherein h is 0, 1, or
 2. 17. The method of claim 16, wherein each R⁷is independently selected from the group consisting of a halide and—(C₁₋₃ alkyl).
 18. The method of claim 1, wherein R² is H.
 19. Themethod of claim 1, wherein the compound of Formula I is selected fromthe group consisting of:N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[1];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[2];5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[3];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[4];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[5];N-((5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[6];5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N,N-dimethylpyridin-3-amine[7];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[8];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[9];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[10];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[11];5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N-isopropylpyridin-3-amine[12];1-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[13];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[14];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[15];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide [16];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[17];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[18];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[19];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[20];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[21];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[22];N-benzyl-1-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[23];1-cyclopentyl-N-((5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[24]; 5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[25];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[26];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[27];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[28];5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[29];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[30];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[31];N-((5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[32];5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N,N-dimethylpyridin-3-amine[33];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[34];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[35];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[36];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[37];5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N-isopropylpyridin-3-amine[38];1-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[39];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[40];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[41];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[42];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[43];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[44];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[45];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[46];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[47];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[48];N-benzyl-1-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[49];1-cyclopentyl-N-((5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[50];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[51];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[52];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[53];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[54];5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[55];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[56];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[57];N-((5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[58];5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N,N-dimethylpyridin-3-amine[59];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[60];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[61];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[62];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[63];5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N-isopropylpyridin-3-amine[64];1-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[65];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[66];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[67];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[68];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[69];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[70];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[71];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[72];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3yl)cyclopentanecarboxamide[73];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[74];N-benzyl-1-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[75];1-cyclopentyl-N-((5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[76];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[77];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[78];N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[79];3-methyl-N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[80];5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[81];5-(pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[82];5-(4-methylpyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[83];N-((5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[84];N,N-dimethyl-5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[85];N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[86];N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[87];2-phenyl-N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[88];N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[89];N-isopropyl-5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[90];N,N-dimethyl-1-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[91];3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[92];5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[93];3,3-dimethyl-N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[94];N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[95];N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[96];N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[97];N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[98];N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[99]; andN-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[100]; or a pharmaceutically acceptable salt thereof.
 20. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-benzyl-1-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[101];1-cyclopentyl-N-((5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[102];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[103];3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[104];N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[105];3-methyl-N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[106];5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[107];5-(pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[108];5-(4-methylpyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[109];N-((5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[110];N,N-dimethyl-5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[111];N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[112];N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[113];2-phenyl-N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[114];N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[115];N-isopropyl-5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[116];N,N-dimethyl-1-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[117];3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[118];5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[119];3,3-dimethyl-N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[120];N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[121];N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[122];N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[123];N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[124];N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[125];N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[126];N-benzyl-1-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[127];1-cyclopentyl-N-((5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[128];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[129];3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[130];N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[131];3-methyl-N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[132];5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[133];3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[134];5-(4-methylpyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[135];N-((5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[136];N,N-dimethyl-5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[137];N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[138];N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[139];2-phenyl-N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[140];N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[141];N-isopropyl-5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[142];N,N-dimethyl-1-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[143];3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[144];5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[145];3,3-dimethyl-N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[146];N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[147];N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[148];N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[149];N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[150];N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[151];N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[152];N-benzyl-1-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[153];1-cyclopentyl-N-((5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[154];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[155];3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[156];N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[157];3-methyl-N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[158];5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[159];3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[160];5-(4-methylpyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[161];N-((5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[162];N,N-dimethyl-5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[163];N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[164];N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[165];2-phenyl-N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[166];N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[167];N-isopropyl-5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[168];N,N-dimethyl-1-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[169];3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[170];3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[171];3,3-dimethyl-N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[172];N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[173];N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[174];N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[175];N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[176];N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[177];N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[178];N-benzyl-1-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[179];1-cyclopentyl-N-((5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[180];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[181];3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[182];N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[183];3-methyl-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[184];5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[185];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[186];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[187];N-((5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[188];N,N-dimethyl-5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[189];N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[190];N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[191];N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[192];N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[193];N-isopropyl-5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[194];N,N-dimethyl-1-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[195];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[196];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[197];3,3-dimethyl-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[198];N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[199]; andN-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[200]; or a pharmaceutically acceptable salt thereof.
 21. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[201];N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[202];N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[203];N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[204];N-benzyl-1-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[205];1-cyclopentyl-N-((5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[206];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[207];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[208];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[209];3-methyl-N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[210];5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[211];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[212];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[213];N-((5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[214];N,N-dimethyl-5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[215];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[216];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[217];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[218];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[219];N-isopropyl-5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[220];N,N-dimethyl-1-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[221];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine [222];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine [223];3,3-dimethyl-N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[224];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[225];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[226];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[227];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[228];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[229];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[230];N-benzyl-1-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[231];1-cyclopentyl-N-((5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[232];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[233];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[234];N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[235];3-methyl-N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[236];5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[237];5-(pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[238];5-(4-methylpyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[239];N-((5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[240];N,N-dimethyl-5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[241];N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[242];N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[243];2-phenyl-N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[244];N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[245];N-isopropyl-5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[246];N,N-dimethyl-1-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[247];5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[248];5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[249];3,3-dimethyl-N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[250];N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[251];N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[252];N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[253];N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[254];N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[255];N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[256];N-benzyl-1-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[257];1-cyclopentyl-N-((5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[258];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[259];5-(pyrimidin-5-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[260];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[261];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[262];5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[263];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[264];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[265];N-((5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[266];5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N,N-dimethylpyridin-3-amine[267];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[268];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[269];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[270];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[271];5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N-isopropylpyridin-3-amine[272];1-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[273];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[274];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[275];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[276];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[277];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[278];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[279];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[280];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[281];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[282];N-benzyl-1-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[283];1-cyclopentyl-N-((5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[284];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine [285];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[286];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[287];3-methyl-N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[288];5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[289];5-(pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[290];5-(4-methylpyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[291];N-((5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[292];N,N-dimethyl-5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[293];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[294];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[295];2-phenyl-N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[296];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[297];N-isopropyl-5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[298];N,N-dimethyl-1-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[299]; and5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[300]; or a pharmaceutically acceptable salt thereof.
 22. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[301];3,3-dimethyl-N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[302];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[303];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[304];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[305];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[306];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[307];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[308];N-benzyl-1-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[309];1-cyclopentyl-N-((5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[310];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[311];5-(pyrimidin-5-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[312];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[313];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[314];5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[315];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[316];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[317];N-((5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[318];5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N,N-dimethylpyridin-3-amine[319];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[320];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[321];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[322];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[323];5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N-isopropylpyridin-3-amine[324];1-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[325];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[326];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[327];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[328];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[329];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[330];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[331];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[332];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[333];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[334];N-benzyl-1-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[335];1-cyclopentyl-N-((5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[336];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[337];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[338];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[339];3-methyl-N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[340];5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[341];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[342];5-(4-methylpyridin-3-yl)-3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[343];N-((5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[344];N,N-dimethyl-5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[345];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[346];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[347];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[348];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[349];N-isopropyl-5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[350];N,N-dimethyl-1-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[351];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[352];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[353];3,3-dimethyl-N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[354];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[355];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[356];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[357];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[358];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[359];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[360];N-benzyl-1-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[361];1-cyclopentyl-N-((5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[362];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[363];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[364];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[365];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[366];1-(5-(2-(5-(5-aminopyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[367];1-(5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[368];1-(5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[369];1-(5-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[370];1-(5-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[371];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[372];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[373];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[374];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[375];1-(5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[376];1-(5-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[377];1-(5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[378];1-(5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[379];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[380];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[381];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[382];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[383];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[384];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[385];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[386];1-(5-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[387];1-(5-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[388];1-(5-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[389];1-(5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[390];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolol3,4-b 1pyridin-5-yl)pyridin-3-yl)propionamide [391];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[392];N-(3-(2-(5-(5-aminopyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[393];N-(3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[394];N-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo-yl)benzyl)methanesulfonamide[395];N-(3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[396];N-(3-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[397];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[398];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[399]; andN-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[400]; or a pharmaceutically acceptable salt thereof.
 23. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[401];N-(3-fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[402];N-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[403];N-(3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[404];N-(3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[405];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[406];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[407];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[408];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[409];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[410];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[411];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[412];N-(3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[413];N-(3-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[414];N-(3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[415];N-(3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo-yl)benzyl)methanesulfonamide[416];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[417];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[418];N¹-(3-(2-(5-(5-aminopyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[419];N¹-(3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[420];N¹-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[421];N¹-(3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[422];N¹-(3-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[423];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[424];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[425];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[426];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[427];N¹-(3-fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[428];N¹-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[429];M-(3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[430];N^(I)-(3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[431];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[432];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[433];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[434];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[435];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[436];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[437];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[438];M-(3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[439];N^(I)-(3-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[440];N^(I)-(3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[441];N^(I)-(3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[442];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[885];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[886];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[887];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[888];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[889];1-(6-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[890];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[891];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[892];N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[893];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[894];2-((5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[895];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-methoxyl)yridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[896];5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[897];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[898];2-cyclohexyl-N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[899]; and3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[900]; or a pharmaceutically acceptable salt thereof.
 24. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[901];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[902];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[903];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[904];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[905];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[906];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[907]; 1-(6-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[908];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[909];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[910];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[911];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[912];2-((5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[913];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-methoxyl)yridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[914];5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[915];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[916];2-cyclohexyl-N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[917];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[918];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[919];3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[920];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[921];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[922];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[923];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[924];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[925];1-(6-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[926];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[927];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[928];N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[929];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[930];2-((5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[931];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-methoxyl)yridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[932];5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[933];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[934];2-cyclohexyl-N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[935];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[936];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[937];3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[938];5-(piperidin-4-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[939];3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[940];5-(1H-pyrazol-4-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[941];5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(pyridin-3-yl)-1H-imidazop,5-clpyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[942];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[943];1-(6-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[944];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[945];5-(5-(piperidin-4-yloxy)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[946];2-(piperidin-4-yl)-N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin5-yl)pyridin-3-yl)acetamide[947];3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[948];N,N-dimethyl-2-((5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine[949];5-(5-methoxyl)yridin-3-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[950];5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[951];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[952];2-cyclohexyl-N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[953];3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[954];5-(pyridin-2-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[955];5-(pyrazin-2-yl)-3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[956];5-(piperidin-4-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[957];3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[958];5-(1H-pyrazol-4-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[959];5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(pyridin-4-yl)-1H-imidazop,5-clpyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[960];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(pyridin-4-yl)-1H-imidazop,5-clpyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[961];1-(6-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[962];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[963];5-(5-(piperidin-4-yloxy)pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[964];2-(piperidin-4-yl)-N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[965];3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[966];N,N-dimethyl-2-((5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine[967];5-(5-methoxyl)yridin-3-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[968];5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[969];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[970];2-cyclohexyl-N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[971];5-(pyridin-4-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[972];5-(pyridin-2-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[973];5-(pyrazin-2-yl)-3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[974];5-(piperidin-4-yl)-3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[975];3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[976];5-(1H-pyrazol-4-yl)-3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[977];5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(pyridin-2-yl)-1H-imidazop,5-clpyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[978];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(pyridin-2-yl)-1H-imidazop,5-clpyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[979];1-(6-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[980];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[981];5-(5-(piperidin-4-yloxy)pyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[982];2-(piperidin-4-yl)-N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[983];3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[984];N,N-dimethyl-2-((5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine[985];5-(5-methoxyl)yridin-3-yl)-3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[986];5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[987];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[988];2-cyclohexyl-N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[989];3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[990];5-(pyridin-2-yl)-3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[991];5-(pyrazin-2-yl)-3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[992];3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[993];3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[994];3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[995];5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(piperidin-1-yl)-1H-imidazop,5-clpyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[996];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[997];1-(6-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[998];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[999]; and3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1000]; or a pharmaceutically acceptable salt thereof.
 25. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1001];3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1002];N,N-dimethyl-2-((5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine[1003];5-(5-methoxyl)yridin-3-yl)-3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1004];5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1005];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1006];2-cyclohexyl-N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1007];3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1008];3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1009];3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1010];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1011];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1012];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1013];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1014];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1015]; 1-(6-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[1016];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1017];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1018];N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1020];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1021];N,N-dimethyl-2-((5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine[1022];5-(5-methoxyl)yridin-3-yl)-3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1022];5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1023];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1024];2-cyclohexyl-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1025];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1026];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1027];3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1028];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1029];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1030];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1031];5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1032];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1033];1-(6-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[1034];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1035];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1036];N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1037];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1038];N,N-dimethyl-2-((5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine[1039];5-(5-methoxyl)yridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1040];5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1041];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1042];2-cyclohexyl-N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1043];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1044];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1045];3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1046];5-(piperidin-4-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1047];5-(1,2,3,6-tetrahydropyridin-4-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1048];5-(1H-pyrazol-4-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1049];5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1050];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1051]; 1-(6-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[1052];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1053];5-(5-(piperidin-4-yloxy)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1054];2-(piperidin-4-yl)-N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1055];5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1056];N,N-dimethyl-2-((5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine[1057];5-(5-methoxyl)yridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1058];5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1059];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1060];2-cyclohexyl-N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1061];5-(pyridin-4-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1062];5-(pyridin-2-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1063];5-(pyrazin-2-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1064];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1065];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1066];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1067];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1068];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(furan-3-yl)-1H-imidazop,5-clpyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1069];1-(6-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[1070];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1071];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1072];N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1073];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1074];2-((5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[1075];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-methoxyl)yridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1076];5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1077];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1078];2-cyclohexyl-N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1079];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1080];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1081];3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1082];5-(piperidin-4-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1083];5-(1,2,3,6-tetrahydropyridin-4-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1084];5-(1H-pyrazol-4-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1085];5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(thiophen-2-yl)-1H-imidazop,5-clpyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1086];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1087];1-(6-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[1088];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1089];5-(5-(piperidin-4-yloxy)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1090];2-(piperidin-4-yl)-N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1091];5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1092];N,N-dimethyl-2-((5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine[1093];5-(5-methoxyl)yridin-3-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1094];5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1095];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1096];2-cyclohexyl-N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1097];5-(pyridin-4-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1098];5-(pyridin-2-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1099]; and5-(pyrazin-2-yl)-3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1100]; or a pharmaceutically acceptable salt thereof.
 26. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1101];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1102];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1103];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1104];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1105];1-(6-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[1106];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1107];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1108];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1109];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1110];2-((5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[1111];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-methoxyl)yridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1112];5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1113];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1114];2-cyclohexyl-N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1115];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1116];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1117];3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1118];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1119];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1120];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1121];5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1122];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1123];1-(6-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[1124];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1125];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1126];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1127];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1128];N,N-dimethyl-2-((5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)ethan-1-amine[1129];5-(5-methoxyl)yridin-3-yl)-3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1130];5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1131];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1132];2-cyclohexyl-N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1133];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1134];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1135];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1136];1-(5-(2-(5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1137];1-(5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yDethan-1-one[1138];1-(5-(2-(5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1139];1-(5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1140];1-(5-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1141];1-(5-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1142];1-(5-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1143];1-(5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1144];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1145];1-(5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1146];1-(5-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1147];1-(5-(2-(5-(5-methoxyl)yridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1148];1-(5-(2-(5-(5-hydroxyl)yridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yDethan-1-one[1149];1-(5-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1150];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-cyclohexylacetamide[1151];1-(5-(2-(5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1152];1-(5-(2-(5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1153];1-(5-(2-(5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethan-1-one[1154];N-(3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[1155];N-(3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[1156];N-(3-(2-(5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[1157];N-(3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[1158];N-(3-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[1159];N-(3-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[1160];N-(3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[1161];N-(3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[1162];N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H--pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1163];N-(3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[1164];N-(3-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[1165];N-(3-fluoro-5-(2-(5-(5-methoxyl)yridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[1166];N-(3-fluoro-5-(2-(5-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[1167];N-(3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorobenzyl)methanesulfonamide[1168];2-cyclohexyl-N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1169];N-(3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[1170];N-(3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[1171];N-(3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[1172];N^(I)-(3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[1173];N^(I)-(3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[1174];N^(I)-(3-(2-(5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[1175];N^(I)-(3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[1176];N^(I)-(3-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[1177];N^(I)-(3-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[1178];N^(I)-(3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[1179];N^(I)-(3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[1180];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H--pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1181];N¹-(3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[1182];N^(I)-(3-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[1183];N^(I)-(3-fluoro-5-(2-(5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[1184];5-(3-(4-(3-((2-(dimethylamino)ethyllamino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1185];N^(I)-(3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenyl)-N²,N²-dimethylethane-1,2-diamine[1186];2-cyclohexyl-N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1187];N^(I)-(3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[1188];N^(I)-(3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[1189];N^(I)-(3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[1190];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[1191];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[1192];5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[1193];2-(3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1194];2-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1195];2-(3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[1196];5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N,N-dimethylpyridin-3-amine[1197];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[1198];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H--pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[1199]; andN-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[1200]; or a pharmaceutically acceptable salt thereof.
 27. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4]pyridin-5-yl)pyridin-3-yl)benzamide[1201];5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N-isopropylpyridin-3-amine[1202];2-(3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[1203];2-(3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1204];2-(3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1205];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[1206];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4]pyridin-5-yl)pyridin-3-yl)butyramide[1207];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4]pyridin-5-yl)pyridin-3-yl)pentanamide[1208];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[1209];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[1210];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[1211];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[1212];2-(3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[1213];2-(3-(2-(5-(5-4(cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[1214];2-(3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[1215];2-(3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1216];2-(3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1217];2-(3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1218];2-(3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1219];2-(3-(2-(5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[1220];2-(3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1221];2-(3-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[1222];1-(6-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)-azetidin-3-amine[1223];2-(3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[1224];2-(3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1225];N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1226];2-(3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1227];2-((5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[1228];2-(3-fluoro-5-(2-(5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1229];5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1230];2-(3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenoxy)-N,N-dimethylethan-1-amine[1231];2-cyclohexyl-N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1232];2-(3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1233];2-(3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenoxy)-N,N-dimethylethan-1-amine[1234];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[1235];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[1236];5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[1237];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1238];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1239];N-((5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)ethanamine[1240];5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N,N-dimethylpyridin-3-amine[1241];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[1242];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[1243];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[1244];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[1245];5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N-isopropylpyridin-3-amine[1246];1-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[1247];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1248];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1249];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[1250];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[1251];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[1252];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[1253];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[1254];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[1255];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[1256];N-benzyl-1-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[1257];1-cyclopentyl-N-((5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[1258];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1259];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[1260];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1261];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1262];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1263];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1264];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1265];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1266];1-(6-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[1267];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1268];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1269];N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1270];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1271];2-((5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[1272];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1273];5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1274];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1275];2-cyclohexyl-N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1276];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1277];3-(4-(3-fluoro-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1278];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[1279];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[1280];3-(2-(5-(5-aminopyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1281];3-fluoro-5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1282];3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1283];3-(2-(5-(5-((ethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1284];3-(2-(5-(5-(dimethylamino)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1285];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[1286];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[1287];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[1288];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[1289];3-fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1290];3-(2-(5-(5-((dimethylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1291];3-fluoro-5-(2-(5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1292];3-fluoro-5-(2-(5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1293];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[1294];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[1295];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[1296];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[1297];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[1298];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[1299]; andN-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[1300]; or a pharmaceutically acceptable salt thereof.
 28. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:3-(2-(5-(5-((benzylamino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1301];3-(2-(5-(5-(((cyclopentylmethyl)amino)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1302];3-(2-(5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1303];3-fluoro-5-(2-(5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1304];3-fluoro-5-(2-(5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1305];3-fluoro-5-(2-(5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1306];3-fluoro-5-(2-(5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1307];3-(2-(5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1308];3-fluoro-5-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1309];3-(2-(5-(1,2-dimethyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1310];3-(2-(5-(6-(3-aminoazetidin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1311];3-(2-(5-(5-(cyclohexyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1312];3-fluoro-5-(2-(5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1313];N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl)acetamide[1314];3-fluoro-5-(2-(5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1315];3-(2-(5-(5-(2-(dimethylamino)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1316];3-fluoro-5-(2-(5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1317];5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1318];3-(2-(5-(5-(benzyloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)-5-fluorophenol[1319];2-cyclohexyl-N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1320];3-fluoro-5-(2-(5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1321];3-fluoro-5-(2-(5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenol[1322];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)propionamide[1323];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[1324];5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[1325];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1326];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1327];N-((5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methypethanamine[1328];5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N,N-dimethylpyridin-3-amine[1329];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[1330];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[1331];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-phenylacetamide[1332];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzamide[1333];5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N-isopropylpyridin-3-amine[1334];1-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-N,N-dimethylmethanamine[1335];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1336];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1337];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3,3-dimethylbutanamide[1338];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[1339];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[1340];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[1341];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[1342];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopentanecarboxamide[1343];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclohexanecarboxamide[1344];N-benzyl-1-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methanamine[1345];1-cyclopentyl-N-((5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methyl)methanamine[1346];5-(5-((3,3-difluoropyrrolidin-1-yl)methyl)pyridin-3-yl)-3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1347];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine[1348];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1349];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1350];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1351];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1352];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1353];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1354];1-(6-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyrazin-2-yl)azetidin-3-amine[1355];5-(5-(cyclohexyloxy)pyridin-3-yl)-3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1356];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1357];N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(piperidin-4-yl(acetamide[1358];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1359];2-((5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)oxy)-N,N-dimethylethan-1-amine[1360];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-methoxypyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1361];5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[1362];5-(5-(benzyloxy)pyridin-3-yl)-3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H--pyrazolo[3,4-b]pyridine[1363];2-cyclohexyl-N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1364];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[1365];3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1366];2-(dimethylamino)-N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1367];2-(dimethylamino)-N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1368];2-(dimethylamino)-N-(5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1369];2-(dimethylamino)-N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl(acetamide[1370];2-(dimethylamino)-N-(5-(3-(4-(pyridin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl(acetamide[1371];2-(dimethylamino)-N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl(acetamide[1372];2-(dimethylamino)-N-(5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1373];2-(dimethylamino)-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1374];2-(dimethylamino)-N-(5-(3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1375];2-(dimethylamino)-N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1376];2-(dimethylamino)-N-(5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1377];2-(dimethylamino)-N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1378];2-(dimethylamino)-N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1379];2-(dimethylamino)-N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1380];N-(5-(3-(4-(5-acetylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-2-(dimethylamino)acetamide[1381];2-(dimethylamino)-N-(5-(3-(4-(3-fluoro-5-(methylsulfonamidomethyl)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1382]; 2-(dimethylamino)-N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1383];2-(dimethylamino)-N-(5-(3-(4-(3-(2-(dimethylamino)ethoxy)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1384];2-(dimethylamino)-N-(5-(3-(4-(3-fluoro-5-(2-(pyrrolidin-1-ypethoxy)phenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1385];2-(dimethylamino)-N-(5-(3-(4-(3-fluoro-5-hydroxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1386];2-(dimethylamino)-N-(5-(3-(4-(3-fluoro-5-methoxyphenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)acetamide[1387]; 4-4245-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)morpholine[1388];3-(4-(4,4-difluoropiperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1389];3-(4-(1-methylpiperidin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1390];4-(2-(5-(5-fluoropyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)morpholine[1391];5-(5-fluoropyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1392];3-(4-(4,4-difluoropiperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-fluoropyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[1393];5-(5-fluoropyridin-3-yl)-3-(4-(1-methylpiperidin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1394];5-(5-fluoropyridin-3-yl)-3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1395];4-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)morpholine[1396];3-(4-(4,4-difluoropiperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1397];5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(1-methylpiperidin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1398];4-(2-(5-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)morpholine[1399]; 5-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(4-(4-methylpiperazin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1400];5-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(4-(4,4-difluoropiperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1401];5-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(4-(1-methylpiperidin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1402];5-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1403];4-(2-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)morpholine[1404];3-(4-(4,4-difluoropiperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[1405]; and5-(1-methyl-1H-pyrazol-4-yl)-3-(4-(1-methylpiperidin-4-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[1046]; or a pharmaceutically acceptable salt thereof.
 29. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[19];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[46];5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[55];N-(5-(3-(4-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)isobutyramide[87];N-((5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)methypethanamine[136];N-(5-(3-(4-(pyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[148];N,N-dimethyl-5-(3-(4-(piperidin-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[163];3-methyl-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[184];5-(4-methylpyridin-3-yl)-3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[239];N-(5-(3-(4-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butyramide[251];5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N-isopropylpyridin-3-amine[272];N,N-dimethyl-5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[293];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[305];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[314];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[320];5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[341];N-(5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ypisobutyramide[347];3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-1-ylmethyl)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[353];1-(5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[368];N-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[395];N^(I)-(3-fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[428];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[434];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridine[885];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[887];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[888];5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[889];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(5-(piperidin-4-yloxy)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine[892];5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-ol[897];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine[900]; and3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine[902]; or a pharmaceutically acceptable salt thereof.
 30. The method ofclaim 1, wherein the compound of Formula I is selected from the groupconsisting of:N-(5-(3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[19];N-(5-(3-(4-(4-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclobutanecarboxamide[46];5-(3-(4-(2-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[55];3-methyl-N-(5-(3-(4-(4-methyl-1H-imidazol-1-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)butanamide[184];5-(3-(4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-N-isopropylpyridin-3-amine[272];N-(5-(3-(4-(thiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)cyclopropanecarboxamide[305];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)-3-methylbutanamide[314];N-(5-(3-(4-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide[320];5-(3-(4-(5-methylthiophen-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-amine[341];1-(5-(2-(5-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)thiophen-2-yl)ethanone[368];N-(3-fluoro-5-(2-(5-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)benzyl)methanesulfonamide[395];N^(I)-(3-fluoro-5-(2-(5-(5-(isopropylamino)pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-yl)phenyl)-N²,N²-dimethylethane-1,2-diamine[428];N-(5-(3-(4-(3-((2-(dimethylamino)ethyl)amino)-5-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pentanamide[434];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[887];3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridine[888]; and5-(1,2-dimethyl-1H-imidazol-5-yl)-3-(4-(3-fluorophenyl)-1H-imidazo[4,5-c]pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine[889]; or a pharmaceutically acceptable salt thereof.
 31. The method ofclaim 1, wherein the fibrotic disorder is a skin fibrosis.
 32. Themethod of claim 1, wherein the fibrotic disorder is scleroderma.
 33. Themethod of claim 1, wherein the fibrotic disorder is pulmonary fibrosis.34. The method of claim 1, wherein the fibrotic disorder is renalfibrosis.
 35. The method of claim 1, wherein the fibrotic disorder isidiopathic pulmonary fibrosis (IPF).
 36. The method of claim 1, whereinthe fibrotic disorder is cirrhosis of the liver.
 37. The method of claim1, wherein the fibrotic disorder is liver fibrosis.
 38. The method ofclaim 1, wherein the subject is a human.